Methods of using high intensity focused ultrasound to form an ablated tissue area containing a plurality of lesions

ABSTRACT

A device and method for ablating tissue is disclosed comprising the steps of acquiring an anatomical image of a patient, correlating the image to the patient, guiding an ablating member within the patient while tracking the position of the ablating member in the patient, positioning the ablating member in a desired position to ablate tissue, emitting ablating energy from the ablating member to form an ablated tissue area and removing the ablating member from the patient.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/956,600, filed Dec. 2, 2015, now allowed, which is a division of U.S.patent application Ser. No. 12/772,437, filed May 3, 2010, now U.S. Pat.No. 9,227,088, which is a division of U.S. patent application Ser. No.11/754,045, filed May 25, 2007, which claims priority to U.S.Provisional Patent Application No. 60/808,306, filed May 25, 2006.

FIELD OF THE INVENTION

The present invention relates generally to the treatment of tissue of apatient with ablative energy and, more particularly, to the ablation oftissue using image guidance.

BACKGROUND OF THE INVENTION

When ablative energy, e.g., high intensity focused ultrasound (HIFU)energy, radiofrequency (RF) energy, microwave energy and/or laserenergy, is applied to tissue, significant physiological effects may beproduced in the tissue resulting from thermal and/or mechanical changesor effects in the tissue. Thermal effects include heating of the tissue;and, when the tissue is heated to a sufficiently high temperature,tissue damage such as coagulative necrosis can be produced. In order toproduce thermal effects in tissue, ablating members, e.g., ultrasoundemitting members such as transducers or electrodes, have been used toemit ablative energy which is applied to tissue. For example, ablatingmembers may by positioned adjacent or in contact with the tissue or bycoupling the ablating members to the tissue via a coupling medium,stand-off and/or sheath. By focusing the ablating energy at one or morespecific focusing zones within the tissue, thermal effect can beconfined to a defined location, region, volume or area. Depending on thetype of ablative energy used, the location, region, volume or area thatis ablated may be remote from the ablating member.

With the use HIFU, one or more focusing zones at or within a designatedtarget location, region, volume or area within a larger mass, body orarea of tissue can be subjected to high intensity ultrasound energywhile tissue surrounding the target area is subjected to much lowerintensity ultrasound energy. In this manner, tissue in the target areacan be heated to a sufficiently high temperature so as to cause adesired thermal effect such as tissue damage, ablation, coagulation,denaturation, destruction or necrosis while tissue surrounding thetarget area is not heated to damaging temperatures and, therefore, ispreserved. Heating of tissue in a target location, volume, region orarea to an ablative temperature creates an ablative lesion in the tissuein the target location, volume, region or area that is desirable in thetreatment of various medical conditions, disorders or diseases. Forexample, the lesion may remain as tissue having altered characteristicsor may be naturally degraded and absorbed by the patient's body andthusly eliminated such that the remaining body, mass or area of tissueis of smaller volume or size due to the absence of the ablated tissue.

The use of HIFU to eliminate tissue or to alter the characteristics oftissue in a target location, volume, region or area within a largermass, body or area of tissue presents many advantages includingminimization of trauma and pain for the patient, elimination of the needfor a surgical incision, stitches and exposure of internal tissue,avoidance of damage to tissue other than that which is to be treated,altered or removed, lack of a harmful cumulative effect from theultrasound energy on the surrounding non-target tissue, reduction intreatment costs, elimination of the need in many cases for generalanesthesia, reduction of the risk of infection and other complications,avoidance of blood loss, and the ability for high intensity focusedultrasound procedures to be performed in non-hospital sites and/or on anout-patient basis.

The action of the heart is known to depend on electrical signals withinthe heart tissue. Occasionally, these electrical signals do not functionproperly, thereby causing heart arrhythmias. Heart arrhythmias, such asatrial fibrillation, have been treated by surgery. For example, asurgical procedure called the “Maze” procedure was designed to eliminateatrial fibrillation permanently. The procedure employs incisions in theright and left atria which divide the atria into electrically isolatedportions which in turn results in an orderly passage of thedepolarization wave front from the sino-atrial node (SA node) to theatrial-ventricular node (AV node) while preventing reentrant wave frontpropagation. Although successful in treating AF, the surgical Mazeprocedure is quite complex and is currently performed by a limitednumber of highly skilled cardiac surgeons in conjunction with otheropen-heart procedures. As a result of the complexities of the surgicalprocedure, there has been an increased level of interest in proceduresemploying ultrasound devices or other types of ablation devices, e.g.thermal ablation, microwave ablation, RF ablation, cryo-ablation or thelike to ablate tissue along pathways approximating the incisions of theMaze procedure. Electrosurgical systems for performing such proceduresare described in U.S. Pat. No. 5,916,213 to Haissaguerre, et al., U.S.Pat. No. 5,957,961 to Maguire, et al. and U.S. Pat. No. 5,690,661, allincorporated herein by reference in their entireties. Procedures arealso disclosed in U.S. Pat. No. 5,895,417 to Pomeranz, et al, U.S. Pat.No. 5,575,766 to Swartz, et al., U.S. Pat. No. 6,032,077 to Pomeranz,U.S. Pat. No. 6,142,994 to Swanson, et al. and U.S. Pat. No. 5,871,523to Fleischman, et al., all incorporated herein by reference in theirentireties. Cryo-ablation systems for performing such procedures aredescribed in U.S. Pat. No. 5,733,280 to Avitall, also incorporatedherein by reference in its entirety. High intensity focused ultrasoundsystems for performing such procedures are described in U.S. PatentApplication Publication No. 2005/0080469 to Larson et al. and U.S. Pat.No. 6,858,026 to Sliwa et al., U.S. Pat. No. 6,840,936 to Sliwa et al.,U.S. Pat. No. 6,805,129 to Pless et al. and No. 6,805,128 to Pless etal., all incorporated herein by reference in their entireties.

High intensity focused ultrasound is an attractive surgical ablationmodality as the energy can be focused to create heat at some distancefrom the ablating member (or transducer). In epicardial applications,most of the heat loss is to the blood, which is also some distance fromthe transducer. This is in contrast to most other technologies, in whichheating occurs close to the ablating element (or electrode) and deeperheating is by thermal conduction. Additionally, since the coronaryarteries are typically towards the epicardial surface, they aretheoretically less susceptible to heating and subsequent constriction bya device such as a HIFU device, which can generate heat deep within themyocardium. For example, a non-irrigated RF epicardial ablationapproaches has the highest heating occurring at the epicardial surface.Any transfer of heat to the deeper endocardium is by thermal conduction.Irrigated RF epicardial ablation approaches allow the heat to penetratedeeper into the tissue, but tend to be limited in depth. In contrast, aHIFU approach can focus the energy to generate heat deeper within thetissue at a substantial distance from the transducer.

Another therapeutic method to terminate AF is to ablate an area that issufficiently large enough such that there is not enough critical mass tosustain the reentrant waveform characteristic of the arrhythmia.

In conjunction with the use of ablation devices, various controlmechanisms have been developed to control delivery of ablation energy toachieve the desired result of ablation, i.e. killing of cells at theablation site while leaving the basic structure of the organ to beablated intact. Such control systems may include measurement oftemperature and/or impedance at or adjacent to the ablation site, as aredisclosed in U.S. Pat. No. 5,540,681 to Struhl, et al., incorporatedherein by reference in its entirety.

Additionally, there has been substantial work done toward assuring thatthe ablation procedure is complete, i.e. that the ablation extendsthrough the thickness of the tissue to be ablated, before terminatingapplication of ablation energy. This desired result is some timesreferred to as a “transmural” ablation. For example, detection of adesired drop in electrical impedance at the electrode site as anindicator of transmurality is disclosed in U.S. Pat. No. 5,562,721 toMarchlinski et al., incorporated herein by reference in its entirety.Alternatively, detection of an impedance rise or an impedance risefollowing an impedance fall are disclosed in U.S. Pat. No. 5,558,671 toYates and U.S. Pat. No. 5,540,684 to Hassler, respectively, alsoincorporated herein by reference in their entireties.

Sometimes ablation is necessary only at discrete positions along thetissue. This is the case, for example, when ablating accessory pathways,such as in Wolff-Parkinson-White syndrome or AV nodal reentranttachycardias. At other times, however, ablation is desired along a line,called linear ablation. This is generally the case for atrialfibrillation, where the aim is to reduce the total mass of electricallyconnected atrial tissue below a threshold believed to be critical forsustaining multiple reentry wavelets. Linear lesions are created betweenelectrically non-conductive anatomic landmarks to reduce the contiguousatrial mass.

Various approaches have been employed to create elongated lesions usingablation devices. The first approach is simply to create a series ofshort lesions using an ablating member, e.g., an electrode, moving italong the surface of the organ wall to be ablated to create a linearlesion. This can be accomplished either by making a series of lesions,moving the ablating member between lesions or by dragging the ablatingmember along the surface of the organ to be ablated and continuouslyapplying ablation energy, e.g., as described in U.S. Pat. No. 5,897,533to Mulier, et al., incorporated herein by reference in its entirety.

A second approach to creation of elongated lesions is simply to employan elongated ablating member, e.g., an elongated electrode, and to placethe elongated ablating member along the desired line of lesion along thetissue. This approach is described in U.S. Pat. No. 5,916,213, citedabove. A third approach to creation of elongated lesions is to provide aseries of ablating elements, e.g., a series of spaced-apart band or coilelectrodes, and arrange the series of ablating elements along thedesired line of lesion. After the ablating portion of the ablationdevice has been properly positioned, the ablating elements are energizedsimultaneously or one at a time to create the desired lesion. If theablating elements are close enough together the lesions can run togethersufficiently to create a continuous linear lesion. Electrodes that maybe activated individually or in sequence, are disclosed in U.S. Pat. No.5,957,961, also cited above. In the case of multi-ablating elementdevices, individual feedback regulation of ablated energy applied viathe ablating elements may also be employed.

A method used for guidance for various medical devices in minimallyinvasive and robotic surgery, e.g., cardiothoracic surgery, is that ofendoscopic visualization. Images from endoscopic light guides andcameras placed within a patient's body, e.g., the patient's thoraciccavity, may be displayed on a video monitor that is viewed by a surgeon.The effective use of an endoscopic visualization method depends on therebeing sufficient open space within the working area of the body. Variousretractors and tissue spreading instruments are sometimes used to holdtissues away from the working field within the body. Pressurized gas orgasses may be introduced into the thoracic cavity to help create spacein which to work with a sufficient field of view. A lung may be deflatedto drop it away from the working field. Without sufficient space andfield of view, it is difficult for the surgeon to recognize theanatomical location and identity of structures viewed on the videodisplay. The requirement for space surrounding the working field has theeffect of limiting the regions which can be safely and confidentlyaccessed by minimally invasive endoscopic techniques. For example, it isvery difficult for the surgeon to endoscopically visualize the passageof instruments through the spaces posterior to and around portions ofthe heart such as the transverse and oblique sinuses. Due to theselimitations, some procedures have not been attempted using minimallyinvasive endoscopic techniques. Other methods or techniques that may beused for guidance or navigation of various surgical instruments inminimally invasive medical procedures, include electromagnetic methods,electric field methods and ultrasound methods.

SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to ablate tissueusing navigation or guidance and, more particularly, to treat AF usingablation and navigation or guidance.

It is also an object of the present invention is to utilize ablation andnavigation or guidance to perform one or more lesions of a Mazeprocedure.

Another object of the present invention is to utilize ablation andnavigation or guidance to ablate a substantial portion of the atria inorder to “debulk” the chamber such that the substrate is modifiedsufficiently to prevent the maintenance of AF.

Another object of the present invention is to utilize ablation andnavigation or guidance to ablate the parasympathetic neurons and/or theautonomic ganglia and their regions of innervation of the heart suchthat the neural impulses promoting AF are blocked.

Another object of the present invention is to utilize ablation andnavigation or guidance to ablate specific locations within the heartthat are responsible for initiating arrhythmias. These locations areoften referred to as “triggers”.

Still further, the present invention has as an object to utilizenavigation or guidance to navigate or guide at least a portion of anablation device placed within the esophagus, the trachea, thevasculature and/or in a trans-thoracic approach from outside the chest,for example, to form one or more lesions of a Maze procedure. At least aportion of an ablation device may be placed within the thoracic cavity,for example, intercostally or subcostally as well as by a sub-xiphoidapproach.

It is still another object of the present invention to have an organpositioning system and method that comprises a device that engages organtissue and allows a surgeon to easily position, manipulate, stabilizeand/or hold an organ during a guided or navigated ablation procedure.

It is still another object of the present invention to place a guided ornavigated ablation device on the epicardial surface of the heart andablate tissue. The ablating energy delivered by the device may befocused at a distance from the device to ablate the underlyingmyocardium without affecting the coronary arteries and sinus. Such adevice may be used to ablate the left atrial isthmus, as well as otherlesions, for example Maze-type lesions.

Another object of the present invention is to temporarily andcontrollably start and stop the heart during a guided or navigatedablation procedure. For example, controlled intermittent asystole (CIA)may be used to control or inhibit motion associated with cardiaccontraction such that a relatively stationary volume of cardiac tissuemay be targeted with ablating energy. Cardiac and/or respiration gatingmay also be used during a guided or navigated ablation procedure.

Another object of the present invention is to have an organ positioningsystem and method that comprises a device that engages organ tissue andallows a surgeon to easily position, manipulate, stabilize and/or holdan organ during a controlled intermittent asystole, guided or navigatedablation procedure.

Some of the advantages of the present invention are that varyingintensity levels of ablating energy can be delivered to tissue forvarying periods of time depending on desired ablative effect, theduration of ablating energy delivery or application to the tissue neededto accomplish a desired effect may be relatively brief depending ondesired size for the lesions of the ablated tissue area and/or desiredthermal effect on the tissue, the ablating member used to deliver theablating energy may be stationary or may be movable, or may be amicroprocessor-controlled phased array in order to scan a target areawith ablating energy, a plurality of individual ablated tissue areas canbe formed in the tissue with the ablated tissue areas being separate anddiscontinuous or being contacting, abutting, contiguous or overlappingto form a single continuous ablated tissue area of desired size and/orshape, the ablating member can remain stationary or can be moved alongto scan a target area with ablating energy, the ablating member may bedesigned with a focusing configuration designed to ensure that thelesions of the ablated tissue area have a desired cross-sectional size,begin a desired depth within the tissue and have a desired depth, theablating member may be positioned externally adjacent or in contact withan external surface of the tissue or may be acoustically coupled withthe tissue to form an internal ablated tissue area without damaging thetissue surface and, in particular, a body cavity such as the esophagusor trachea, and an ablated tissue area of definitive size can berepeatedly and consistently produced. The esophagus is close to theposterior of the left atrium of the heart. This position makes itparticularly attractive for trans-esophageal echocardiography (TEE)imaging as well as trans-esophageal ultrasound ablation.

The ablating elements of a phased array may be electronically controlledsuch that individual ablating elements can be controlled to interferewith the adjacent ablating elements. This interference, for example, canbe used to “steer” the focal point of an acoustical energy to virtuallyany spot. For example, each element may be independently controlled andenergized slightly out of phase with one another to electronically steerthe focal point.

These and other objects, advantages and benefits are realized with thepresent invention as generally characterized in a method of tissueablation using guidance or navigation. Ablating energy may be focusedwithin the tissue at one or more overlapping or non-overlapping focusingzones contained in a target area. If multiple focusing zones aredesired, the focusing zones may be spaced from one another. The tissueis heated at the focusing zones by the ablating energy, thereby formingan ablated tissue area. Once an ablated tissue area of desired extenthas been obtained, the ablating member may be removed.

An ablating member may have a focusing configuration that causes theablating energy to be focused a predetermined distance from an activeface of the ablating member. Also, the focusing configuration results information of lesions of predetermined or known depth in accordance withthe length of the focusing zones, the selected ablating energyintensities and frequencies and the selected duration times for ablatingenergy delivery. The lesion depths are selected so that the lesions donot extend deeper than desired, thereby avoiding unwanted damage tosurrounding tissue. The plurality of lesions may be non-contacting, witheach lesion surrounded by unablated tissue. One or more of the pluralityof lesions may contact another one of the plurality of lesions. Thecross-sectional size of the lesions and the location and arrangement ofthe focusing zones in the tissue result in formation of a specific sizeablated tissue area having a specific cross-sectional configuration. Asingle, discrete ablated tissue area or a plurality of single, discreteablated tissue areas can be formed in the tissue in a single procedureor treatment performed at one time or in multiple procedures ortreatments performed at different times. Where a plurality of ablatedtissue areas are formed, the ablated tissue areas can be contiguous,contacting, overlapping or in abutment with one another so that theablated tissue areas together form or create a single ablated tissuearea of larger cross-sectional size and/or of a desired cross-sectionalconfiguration.

One aspect of the present invention provides a system for positioning,manipulating, holding, grasping, immobilizing and/or stabilizing anorgan, such as a heart. The system may include one or moretissue-engaging devices, one or more suction sources, one or more fluidsources, one or more ablation devices, one or more sensors and one ormore processors. The system may also include one or more imagingdevices, guidance devices, drug delivery devices and/or illuminationdevices. A tissue-engaging device of the system may comprise atissue-engaging head, a support apparatus and a clamping mechanism forattaching the tissue-engaging device to a stable object, such as aretractor that is fixed to a patient's chest or an operating table. Atissue-engaging device of the system may comprise one or more energytransfer elements connected to an energy source, one or more sensorsconnected to a processor, one or more suction openings connected to asuction source, and/or one or more fluid openings connected to a fluidsource.

Another aspect of the present invention provides a method ofpositioning, manipulating, holding, grasping, immobilizing and/orstabilizing an organ, such as a heart. The method includes engaging andpositioning an organ, such as a heart, during an ablation procedure. Theablation procedure may include intermittently stimulating a vagal nerveand/or pacing a heart. The ablation procedure may include placement of alead on or within a heart. The ablation procedure may include the use ofsuction to engage and position an organ, such as a heart. The ablationprocedure may include the delivery of fluids, gases, and/or agents, suchas drugs.

The foregoing, and other, features and advantages of the invention willbecome further apparent from the following detailed description of thepresently preferred embodiments, read in conjunction with theaccompanying drawings. The detailed description and drawings are merelyillustrative of the invention rather than limiting, the scope of theinvention being defined by the appended claims in equivalence thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a broken perspective view, partly schematic, illustrating ahigh intensity focused ultrasound stimulation or ablation assembly foruse in the methods of the present invention.

FIG. 2 is a broken bottom view of an ultrasound emitting member of afocused ultrasound ablation device of the high intensity focusedultrasound stimulation or ablation assembly.

FIG. 3 is a broken side view, partly in section, of the ultrasoundemitting member and depicting focusing of ultrasound energy in tissue toform an ablated tissue area containing unablated tissue and a pluralityof lesions at which the tissue is ablated.

FIG. 4 is a broken top view illustrating the surface or cross-sectionalconfiguration of the ablated tissue area of FIG. 3.

FIG. 5 is a broken top view illustrating the surface or cross-sectionalconfiguration of an alternative ablated tissue area created in thetissue.

FIG. 6 is a broken top view illustrating the surface or cross-sectionalconfiguration of a plurality of further alternative ablated tissue areascreated in the tissue.

FIG. 7 is a broken top view illustrating the surface or cross-sectionalconfiguration of another alternative ablated tissue area created in thetissue.

FIG. 8 is a broken bottom view of an alternative focused ultrasoundablation device having a modified ultrasound emitting member for use inthe methods of the present invention.

FIG. 9 is a broken top view illustrating the surface or cross-sectionalconfiguration of an additional alternative ablated tissue area formed inthe tissue.

FIG. 10 shows a schematic picture of various transmural lesions of aMaze procedure which can be made with the instrument according to theinvention, and which can block electrical impulses in directionscrosswise to said lesions.

FIG. 11 is a schematic view of one embodiment of a system in accordancewith the present invention.

FIG. 12 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 13 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 14 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 15 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 16 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 17 is a flow diagram of one embodiment of the present invention.

FIG. 18a is a cross-sectional view of a portion of an ultrasoundemitting member of a focused ultrasound ablation device of the highintensity focused ultrasound stimulation or ablation assembly.

FIG. 18b is a bottom view of a portion of an ultrasound emitting memberof a focused ultrasound ablation device of the high intensity focusedultrasound stimulation or ablation assembly.

FIG. 18c is a side view of a portion of an ultrasound emitting member ofa focused ultrasound ablation device of the high intensity focusedultrasound stimulation or ablation assembly.

FIG. 19 is a cross-sectional view of a portion of an ultrasound emittingmember of a focused ultrasound ablation device of the high intensityfocused ultrasound stimulation or ablation assembly.

FIG. 20 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 21 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 22 is an illustration of one embodiment of a medical device in usein accordance with the present invention.

FIG. 23 is a flow diagram of one embodiment of the present invention.

FIG. 24 is a cross-sectional view of a portion of one embodiment of amedical device in accordance with the present invention.

FIG. 25 is a view of a phased array in accordance with one embodiment ofthe present invention.

FIGS. 26a and 26b are illustrations of simulation results of anultrasound field in accordance with one embodiment of the presentinvention.

FIG. 27 is a view of a portion of one embodiment of a medical device inaccordance with the present invention.

FIG. 28 is an exploded view of a portion of one embodiment of a medicaldevice in accordance with the present invention.

FIG. 29 is a diagram of a portion of one embodiment of a medical devicein accordance with the present invention.

FIG. 30 is a graph in accordance with one embodiment of with the presentinvention.

FIGS. 31a and 31b are diagrams of a portion of one embodiment of amedical device in accordance with the present invention.

FIG. 32 is a schematic of a circuit in accordance with one embodiment ofthe present invention.

FIGS. 33a, 33b and 33c are views of a portion of one embodiment of amedical device in accordance with the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The entire content of U.S. patent application Ser. No. 11/754,045 filedMay 25, 2007, and U.S. Provisional Patent Application No. 60/808,306filed May 25, 2006, is hereby incorporated by reference.

One embodiment of an ablation or stimulation assembly or system 10 foruse in the methods of the present invention is illustrated in FIG. 1 andis similar to the HIFU stimulation assembly described in prior U.S.patent application Ser. No. 10/464,213 and U.S. patent application Ser.No. 10/600,871, the disclosures of which are incorporated herein byreference. The high intensity focused ultrasound ablation or stimulationassembly or system 10 includes a focused ultrasound ablation orstimulation device 12, a power supply 14 and a controller 16. Thefocused ultrasound ablation or stimulation device 12 is similar to thatdescribed in U.S. patent application Ser. Nos. 10/464,213 and 10/600,871and includes a focused ultrasound emitting member 18, an elongate handleshaft or body 20 having a distal end at which the ultrasound emittingmember is disposed and a handle or handpiece 22 coupled to a proximalend of the handle shaft 20. As shown in FIGS. 2 and 3, the ultrasoundemitting member includes a transducer 24 carried by or within a housing,carrier or case 26. The transducer, which includes one or moreindividual ultrasound emitting elements or transducer elements, iscapable of generating and emitting ultrasound energy in response tobeing supplied with electrical power from power supply 14. In the caseof ultrasound emitting member 18, the transducer includes a plurality ofindividual ultrasound emitting elements or transducer elements 28, eachincluding a piezoelectric element that vibrates to produce ultrasoundenergy when an electrical potential or signal is supplied thereto. Thetransducer elements 28 have a focusing configuration or geometry thatresults in the ultrasound energy produced thereby being focused a fixeddistance from the ultrasound emitting member. The transducer elements 28have a partial spherical or concave configuration and/or include one ormore lens causing the ultrasound energy generated thereby to be focused,as shown by arrows in FIG. 3, at focusing zones F, respectively.

The transducer elements 28 are arranged in an array on or in housing 26;and, therefore, the transducer 24 may be considered a multi-arraytransducer. In the case of ultrasound emitting member 18, the transducerelements are shown arranged in a planar array of three rows R and sixcolumns C, although the transducer elements can be arranged in anynumber of rows and columns. Alternatively, the transducer elements maybe angled to a more central area to create a lesion of a desired shaperather than in a row aimed along the same axis. In the case of focusedultrasound emitting member 18, each row R has an equal number oftransducer elements, and each column C has an equal number of transducerelements. It should be appreciated that any number of transducerelements can be provided in each row and column and that the number oftransducer elements provided in each row and column can be the same ordifferent. Alternatively, the individual transducer element or elementsmounted in the housing may be of an elongated or linear shape and may belargely aligned parallel with each other. Each of these linear elementswould be capable of producing a line of focused energy.

The transducer elements 28 can be referenced by their location in thearray. For example, the transducer element 28 in the first row, firstcolumn can be designated transducer element R1C1, the transducer element28 in the first row, second column can be designated transducer elementR1C2 and so on. The transducer elements may be disposed as close aspossible to one another; however, it should be appreciated that thespacing between the individual transducer elements 28 of the array canvary so that adjacent transducer elements can be disposed closertogether or further apart from one another. As explained further below,the transducer elements 28 may be selectively, independently actuatableto selectively emit or not emit ultrasound energy.

The transducer elements 28 can be designed in various ways as known inthe art. In the case of transducer 24, the transducer elements eachcomprise a piezoelectric element formed by a layer of piezoelectricmaterial carried by housing 26. The piezoelectric elements are recessedfrom a planar external lower or bottom surface 32 of housing 26. Thepiezoelectric elements are curved in a direction inwardly of surface 32such that ultrasound energy generated by the piezoelectric elements isemitted from focused ultrasound emitting member 18 in a directionperpendicular to surface 32 for focusing at the focusing zones F, whichare spaced outwardly of surface 32. Accordingly, surface 32 is an activesurface or face of the ultrasound emitting member which, when positionedexternally on, adjacent or in contact with tissue S, results in theultrasound energy emitted by the transducer being focused at zones F,which will be disposed within the tissue S as shown in FIG. 3. When theultrasound emitting member is positioned on, against or adjacent thetissue S at a location aligned with a designated target area 34 withinthe tissue S, the target area 34 being shown in dotted lines in FIGS. 3and 4, the focusing zones will be disposed at or within the target areaas best shown in FIG. 3.

Each focusing zone F consists of a single point or a plurality of pointsforming a zone at which the ultrasound energy is focused. Each focusingzone is in line with a central axis of the corresponding transducerelement. Each focusing zone is disposed a fixed predetermined distancefrom a plane containing the active face 32, the predetermined distancefor each focusing zone being perpendicular or normal to the active face32. Therefore, the focusing zones F will also be disposed apredetermined perpendicular distance or a calculable or determinableperpendicular distance from an external surface 36 of tissue S withwhich the active face 32 is placed in contact or adjacent thereto. Wherethe active face 32 is placed in contact with the external tissue surface36, the perpendicular distance that zones F are disposed from externaltissue surface 36 will be the same as the predetermined distance. Wherethe active face 32 is not placed in contact with the external tissuesurface 36 but, rather, is spaced from the external tissue surface 36 bya known amount, for example, the perpendicular distance that zones F aredisposed from the external tissue surface will correspond to thepredetermined distance minus the distance that the active face 32 isspaced from the external tissue surface 36. Where the active face 32 isspaced from the external tissue surface 36, an acoustic coupling mediumcan be disposed between the external tissue surface 36 and the member18. Examples of acoustic coupling mediums are disclosed in U.S. PatentApplication Publication No. 2004/0234453 to Smith and U.S. Pat. No.6,039,694 to Larson et al., both incorporated herein by reference intheir entireties. Acoustic coupling mediums may include stand-offsand/or sheaths, which may contain a gel that can act as a heat sink forcooling and/or as a medium for energy transfer. The stand-offs and/orsheaths may be disposable. For example, a disposable condom-like sheathcould be placed over the device end.

The individual transducer elements, 28 of ultrasound emitting member 18may be individually controlled in a manner to interfere with one anothersuch that the focal zone can be precisely controlled. For example,individual elements can be driven at the same frequency, but differentphases and possibly different amplitudes to form a phased arraytransducer and focus the energy more exactly. The transducers may havevarying focal lengths or frequencies at differing, converging angles. Inone embodiment, a series of two or more transducers may be aimed at thesame focal point but could be alternated on and off to reduce heatgeneration of the transducers and the tissue directly in front of themthus preventing near-field tissue necrosis. This on/off cyclingtechnique would allow a lesion to be made more quickly withoutintermediate tissue damage. In one embodiment of the present invention,an ultrasound conductive cooling field may be created with a coolingliquid, for example, delivered between the transducer elements and thetissue.

Since the ultrasound is focused at focusing zones F, which may be spacedfrom one another, the ultrasound is of greater or higher intensity atfocusing zones F than in tissue surrounding the focusing zones F.Ultrasound energy is thusly focused or concentrated at the focusingzones F, causing the tissue at the focusing zones F to be heated to anablative temperature resulting in formation of lesions 38 at thefocusing zones, respectively. The tissue is ablated at the lesions 38;and, as used herein, “ablated” tissue includes tissue that has beenthermally damaged, altered, necrotized, denatured, destroyed, coagulatedor cauterized. When all of the transducer elements 28 are actuated, asshown in FIG. 3, heating of tissue S will occur at a focusing zone F foreach transducer element, resulting in formation of a lesion 38 at eachfocusing zone F. The cross-sectional size of the lesions will normallydepend on the width of the focusing zones. However, depending on theintensity and duration of the ultrasound energy, the lesions 38 may“grow” or “spread” somewhat beyond the focusing zones due to thermalconduction causing the dispersal or spread of heat from the focusingzones. Therefore, depending on procedural parameters and the dimensionsof the focusing zones, each lesion 38 has a predetermined or predictablecross-sectional size, i.e. length and width, as well as depth. As anexample, each lesion 38 spreads radially outwardly somewhat from thecorresponding focusing zone. The lesions 38 have a generally circularsurface or cross-sectional configuration as shown in FIGS. 3 and 4 and aspecific depth as shown in FIG. 3. Depending on procedural parameters,the dimensions of the focusing zones and/or the type of tissue beingablated, the lesions may or may not have a uniform cross-section alongtheir depth. Where the focusing zones are sufficiently close together,and where the intensity of the ultrasound energy emitted from thetransducer elements is sufficiently high and is applied to the tissuefor a sufficient duration, the individual lesions may merge to form asingle continuous lesion at the target area so that the target area isfilled with ablated tissue. However, depending on the spacing betweenthe focusing zones, and depending on the intensity of the ultrasoundenergy emitted from the transducer elements and the duration ofultrasound energy delivery to the tissue, the lesions 38 may remainseparate, discrete and not connected to one another as shown in FIGS. 3and 4 so that the target area 34 contains unablated tissue and thelesions 38 at which the tissue is ablated. FIG. 4 illustrates a lesion38 formed in tissue S for each focusing zone F wherein the lesions 38are disposed within the target area 34 but do not merge with, contact,overlap or abut one another. Rather, each lesion 38 is surrounded orcircumscribed perimetrically by unablated tissue. The non-contactinglesions 38 and unablated tissue are contained in an ablated tissue area35 at, coincident, coextensive or aligned with the target area 34.

When all of the transducer elements 28 are actuated, an ablated tissuearea of specific surface or cross-sectional configuration and size iscreated within the tissue S for the transducer 24 in accordance with theconfiguration and size of the array, the intensity level of the emittedultrasound energy, the duration or time of ultrasound energy delivery tothe tissue, and the size of the lesions. Accordingly, an ablated tissuearea having a specific cross-sectional length, width and depth is formedin the tissue, with the perimeter of the ablated tissue areacircumscribing the array of lesions 38. FIGS. 3 and 4 illustrate, indotted lines, the ablated tissue area 35 formed in tissue S when all ofthe transducer elements are actuated. The ablated tissue area 35 has agenerally rectangular-surface or cross-sectional configuration or areawith a predetermined cross-sectional length and width shown in FIG. 4and a predetermined cross-sectional depth, shown in FIG. 3, thecross-sectional depth corresponding to the depth of the lesions 38. Whenthe ultrasound emitting member 18 is positioned on, against or adjacentthe tissue S at a location aligned with a designated target area 34, theablated tissue area 35 will be formed at or coincide with the targetarea as shown in FIGS. 3 and 4. The ablated tissue area is surrounded,bordered or circumscribed perimetrically by unablated tissue, as well ashaving unablated tissue above and below it. Since the focusing zones Fbegin the predetermined distance or the calculable or determinabledistance below the tissue surface 36, the ablated tissue area 35 is aninternal or subsurface ablated tissue area beginning the predetermineddistance or the calculable or determinable distance beneath the tissuesurface. Accordingly, the lesions 38 and ablated tissue area 35 begin ata beginning or starting margin 64 located the predetermined orcalculable distance below the external tissue surface 36 and end at anending margin 66 disposed further below the external tissue surface thanthe beginning margin, the distance between the beginning and endingmargins corresponding to the depth of the lesions 38 and, therefore, thedepth of the ablated tissue area 35.

The housing 26 can have various external configurations and sizes andcan be formed by a portion of the transducer or can mount the transducerelements in various ways. The handle shaft 20 comprises an elongate,hollow or tubular member of sufficient length to position the ultrasoundemitting member 18 at various operative sites in or on the body of apatient while the handle 22 is maintained at a remote location,typically externally of the patient's body. The handle shaft 20 could besolid and may comprise a bar or other shaped member. Preferably, thehandle shaft 20 is malleable as disclosed in U.S. patent applicationSer. No. 09/488,844, the disclosure of which is incorporated herein byreference. The handle 22 has a forward end coupled to the proximal endof handle shaft 20 and has a rearward end. The handle 22 preferably hasa configuration to facilitate grasping by a surgeon or other operator.One or more controls or switches 42 may be provided on handle 22 toeffect operation of the focused ultrasound ablation device. The line offocused energy F, may be aligned with the long axis of the entiredevice. Alternatively, the housing 26 may be attached to the handleshaft 20 such that housing 20 may be manually or remotely rotated suchthat the line of focused energy F, is perpendicular to the long axis ofthe device or some angle between perpendicular and parallel to the longaxis of the device.

One or more electrical transmission wires 44 is/are connected to thetransducer 24 and extend through the handle shaft 20 for connection withpower supply 14 in order to transmit or supply electric current from thepower supply to the transducer. The power supply may be disposed partlyor entirely in the handle, or may be provided separately as a console orunit coupled to the handle shaft or the handle via one or moreappropriate transmission wires, which may be the same or different fromthe one or more transmission wires 44. For example, an electrical cordof suitable length may be removably coupled between the handle 22 andthe power supply 14. The power supply 14 can be designed in various waysas a source or supply of electricity to activate or excite transducer 24to generate and emit ultrasound energy. For example, the power supplycan be designed to provide high frequency alternating electrical currentto the transducer via the one or more transmission wires. The powersupply may include a single or multiple channel RF generator, with orwithout an amplifier, providing a current or voltage source to power thetransducer(s). Electrical current provided by the power supply isselectively discharged into all or selected ones of the piezoelectricelements producing vibration of all or selected ones of thepiezoelectric elements and, therefore, producing acoustic or ultrasonicwaves or energy. The power supply may be separate from the handle butmay be operated via controls 42 on the handle. In addition, thetransducer assembly may incorporate air or liquid cooling circulationchannels to remove excess internal heat generated during operation.

Each transducer element, 28 may have slightly different physicalcharacteristics such as efficiency, focal zone, etc. that significantlyaffect performance. These variances can be compensated for by controller16. The handle 22 may have incorporated within it, a memory chip that iscapable of being read by controller 16. The memory chip may storetransducer properties, such as power requirements, temperaturerequirements, number and/or type of transducers, type of device, numberof allowed uses, reuse information, variation in device to devicecharacteristics, etc. that were characterized and recorded duringmanufacture, assembly and/or use. The memory chip may store informationdelivered by controller 16. For example, the controller may deliver adate and time of use stamp to the memory chip and/or details about aprocedure. The controller and/or memory chip may be used to prevent theuse of the device for more times than desired or acceptable. One or morereuse prevention features may be incorporated into ablation system 10.

In the case of focused ultrasound ablation device 12, a transmissionwire 44 is provided for each piezoelectric element and, therefore, foreach transducer element. As shown in FIG. 3, each transmission wire 44is connected to its corresponding piezoelectric element and to the powersupply so that the transducer elements are individually driven by orsupplied with current from the power supply. The transmission wires 44are disposed in respective passages within the housing and may bedisposed within a sheath or sleeve 46 extending through shaft 20.However, the transmission wires can be disposed externally of thehousing and/or the shaft. The transmission wires 44 are connected toswitches (not shown), respectively, for controlling the supply ortransmission of current from the power supply 14 to the piezoelectricelements, respectively. The switches can be incorporated in theultrasound emitting member 18, the power supply 14 and/or the controller16.

The controller or control unit 16 controls the supply of power frompower supply 14 to transducer 24 so that the transducer can be driven todeliver various intensity levels of ultrasound energy for variousdurations, periods or lengths of time. In particular, the controller 16controls the supply of power from the power supply to the individualpiezoelectric elements so that the transducer elements can beindividually driven or actuated to emit ultrasound energy. Thecontroller, which may be designed as part of the power supply, willtypically include a control panel and display monitor, one or moreswitches for current control, an input mechanism such as a keyboard,and/or a microprocessor including memory, storage and data processingcapabilities for performing various functions. The controller is capableof selectively activating the switches for the transducer elements to“fire” or effect actuation of all or selected ones of the plurality oftransducer elements to emit ultrasound energy. For example, switches onthe controller 16 and/or the controller keyboard can be used toselectively couple and decouple the individual transducer elements 28with the electrical drive signal or current from the power supply 14.

Input to the controller 16 provided by the surgeon or other medicalpersonnel determines the transducer elements 28 to be actuated. Forexample, data entered via the controller keyboard is used to identifythe particular transducer elements to be actuated, the transducerelements being identified, for example, by their location or position inthe array as explained above. In this manner, the switches of selectedtransducer elements can be activated to permit transmission ofelectrical current from the power supply to the piezoelectric elementsof the selected transducer elements while the switches of othernon-selected transducer elements can remain deactivated to preventtransmission of electrical current thereto when the power supply isactuated or switched to an “on” mode. It should be appreciated thatvarious components and/or methodology can be incorporated in the device12, the power supply 14 and/or the controller 16 to permit selectiveactuation of selected ones of the transducer elements 28 and that suchcomponents and/or methodology would be within the purview of one skilledin the art. In addition, the precise location to focus ablative energycan be determined by various imaging modalities such as ultrasoundimaging, CT, MRI, PET, fluoroscopy, etc. The coordinates for the desiredarea of ablation from any of these imaging modalities can beelectronically fed to controller 16 such that the desired ablationpattern can be generated and ablated. Two or three-dimensional imagingmay be performed as well as phased or annular array imaging may beperformed. For example, two or three-dimensional echocardiography, suchas transesophageal echocardiography, or ultrasound imaging, such astransthoracic ultrasound imaging may be employed as described in U.S.Patent Application Publication No. 2005/0080469, the disclosure of whichis incorporated by reference in its entirety.

Various transducers can be used in the methods of the present invention.The piezoelectric elements can be made of various piezoelectricmaterials such as PZT crystal materials, hard lead, zirconate/leadtitanium, piezoelectric ceramic, or lithium-niobate piezoceramicmaterial. The transducer elements can be of various sizes and can havevarious focusing geometries. The frequency ranges of the transducers canvary depending on clinical needs. Transducer frequencies may be in therange of 0.5 to 12 MHz and, more typically, in the range of 5 to 12 MHz.Preferably, the transducer frequency will allow thermal ablation of thetissue to be effected in response to the application or delivery ofultrasound energy to the tissue for a relatively short duration orlength of time.

In accordance with the present invention, the duration or length of timefor ultrasound energy delivery or application to the tissue preferablyranges from 2 to 60 seconds depending on desired lesion size and/orablative effect.

In accordance with the methods of the present invention, high intensityfocused ultrasound may used to create an ablated tissue area containingunablated tissue and a plurality of lesions at which the tissue isablated.

As shown in FIG. 3, the ultrasound emitting member 18 is placed againstthe tissue S of a patient to position the active face 32 in contact withthe external tissue surface 36. The active face is placed at or on thesurface 36 at a location aligned with a desired target area 34 in thetissue for creation of an ablated tissue area, such locationcorresponding to an area of the tissue that is to be ablated. The shaft20 may be grasped and manipulated, as necessary, to facilitatepositioning of the active face at the desired location on the externaltissue surface. Typically, the ultrasound emitting member will be placedin contact with tissue at a location where an ablation lesion isdesired. Also, all or specific ones of the transducer elements areselected for actuation or “firing” in accordance with the desired sizeand configuration for the ablated tissue area and/or the desired numberof lesions to be contained in the ablated tissue area. The ablationdevice 12 is programmed via the controller to effect actuation or“firing” of the selected transducer elements when electric current or asignal is supplied to the transducer. Of course, selection andprogramming for actuation or “firing” of selected transducer elementscan be performed prior to positioning of member 18.

Once the active face is positioned at the desired location, the powersupply is activated or switched to an “on” mode to transmit electricalenergy to the previously selected transducer elements. In responsethereto, the piezoelectric elements corresponding to the selectedtransducer elements vibrate and produce ultrasound energy, which isfocused within the tissue S at the corresponding focusing zones F. Inthe procedure of FIG. 3, all of the transducer elements are “fired” toemit ultrasound energy, causing the tissue to be heated to an ablativetemperature at a focusing zone for each transducer element. The tissue Sat the focusing zones is heated to a temperature in the range of 50 to90 degrees Celsius for the time required to achieve ablation or thermaldamage in the tissue. The focusing zones are contained in the targetarea 34. The tissue S is heated at the focusing zones to a sufficientlyhigh temperature so as to cause a plurality of subsurface or internallesions 38 to be simultaneously formed in the tissue S while theultrasound emitting member 18 remains external of and does notphysically penetrate the tissue S.

Lesions 38 have a generally circular surface or cross-sectionalconfiguration as shown in FIGS. 3 and 4 and do not contact or touch oneanother. Lesions 38 contain ablated or damaged tissue while the tissuesurrounding each lesion 38 is not heated to the ablative or thermallydamaging temperature and, therefore, is unablated or undamaged. In thismanner, eighteen discontinuous or non-contacting individual lesions 38are formed in the tissue as represented in FIG. 4. Lesions 38 arecontained in the internal ablated tissue area 35 coincident with thetarget area 34, the ablated tissue area 35 containing the lesions 38 andthe unablated tissue between adjacent lesions 38. The lesions 38 have across-sectional length and width and a depth of known parametersdepending on the size and focusing geometry of the transducer elements,the intensity of the ultrasound energy, the temperature to which thetissue is heated and the duration of ultrasound energy delivery orapplication to the tissue.

Due to the predetermined distance and the known length for the focusingzones, the lesions 38 and, therefore, the ablated tissue area 35, beginat the beginning or starting margin 64 located a predetermined or knowndepth beneath or below the external tissue surface 36 and end at theending margin 66 located a greater predetermined or known depth beneaththe external tissue surface 36, the distance between the beginning andending margins corresponding to the depth of the lesions and, therefore,the depth of the ablated tissue area 35. By selecting the appropriatefocusing zone depth and treatment parameters, a desired thickness ordepth of unablated or undamaged tissue between the beginning margin 64and the external tissue surface 36 is disposed outside the ablatedtissue area. Preferably, the beginning margin is located 50 to 150micrometers below the external tissue surface. In the method of FIGS. 3and 4, a layer of unablated tissue about 100 micrometers thick ismaintained between the external tissue surface 36 and the beginning orstarting margin 64 of the lesions 38. The lesions 38 have a depth of 50to 150 micrometers and, preferably, a depth of about 100 micrometers, inthe direction perpendicular to tissue surface 36 such that the ablatedtissue area and the lesions terminate or end at the ending margin 66disposed a depth of about 200 micrometers beneath the external tissuesurface 36 at the transducer/tissue interface. Accordingly, there is aperpendicular distance of about 200 micrometers from the external tissuesurface to the ending margin of the ablated tissue area. By selectingthe appropriate

focusing zone length and treatment parameters, the depth of the endingmargin 66 within the tissue is controlled.

As shown in FIG. 4, the ablated tissue area 35, which is surroundedabove, below and perimetrically by unablated or undamaged tissue, has asurface or cross-sectional configuration or area of generallyrectangular shape with a cross-sectional width and length varying from 3mm to 50 mm in either dimension, i.e. 3 mm×3 mm to 50 mm×50 mm or inbetween, depending on the size of the area to be treated. Although thecross-sectional length and width or other external dimensions of theablated tissue area can be determined by the locations of the “fired”transducer elements, it should be appreciated that the cross-sectionallength and/or width of the ablated tissue area can alternatively beobtained by moving the member 18 along the tissue as described in U.S.patent application Ser. No. 09/487,705, the disclosure of which isincorporated herein by reference.

Depending on the desired lesion size and/or thermal effect, ultrasoundenergy may be delivered or applied to the tissue for a duration in therange of 2 to 60 seconds. The emission of ultrasound energy byultrasound emitting member 18 is terminated by the surgeon or otheroperator once lesions of desired size or a desired amount of tissueablation has been obtained, and the member 18 is removed. In order toterminate the emission of ultrasound energy by the ultrasound emittingmember, the power supply is deactivated or switched to an “off” mode sothat electrical current is no longer supplied to the selectedpiezoelectric elements.

FIG. 5 is representative of a single treatment procedure in accordancewith the present invention wherein a subsurface ablated tissue area 135containing four non-contacting lesions 138 is formed. The ablated tissuearea 135 is similar to ablated tissue area 35 except that it is ofgenerally square surface or cross-sectional configuration or area andcontains four generally circular lesions 138 each surrounded byunablated tissue. The ablated tissue area 135 can be formed using theultrasound emitting member 18 by selecting and “firing” transducerelements R1C1, R1C2, R2C1 and R2C2, for example, to emit ultrasoundenergy. As described for the procedure illustrated in FIGS. 3 and 4, theultrasound energy emitted by the selectively “fired” or actuatedtransducer elements is focused in the tissue at a focusing zone for eachactuated transducer element, causing subsurface lesions 138 to be formedin the tissue at the focusing zones corresponding to transducer elementsR1C1, R1C2, R2C1 and R2C2. The lesions 138 are similar to lesions 38 butare larger in diametric cross-sectional size than lesions 38. Theablated tissue area 135 is surrounded by unablated tissue above, belowand perimetrically.

FIG. 6 is representative of a multiple treatment procedure in accordancewith the present invention wherein a plurality of internal ablatedtissue areas 235, each containing unablated tissue and a plurality oflesions 238, are formed or created in the tissue S. The ablated tissueareas 235 are spaced from one another, and each contains two generallycircular lesions 238 similar to lesions 138 except that lesions 238 havea slightly larger cross-sectional diameter than lesions 138. The lesions238 of each ablated tissue area 235 are spaced slightly from one anotherand are surrounded by unablated tissue so as to be non-contacting. Eachablated tissue area 235 has a surface or cross-sectional configurationor area of generally rectangular shape. The ablated tissue areas 235,which are similar to ablated tissue area 35 except for theircross-sectional configuration, can be formed using member 18 asdescribed above by actuating an appropriate pair of transducer elements.The ablated tissue areas 235 are typically formed in separate treatmentsperformed at different times. However, it should be appreciated that aplurality of ablated tissue areas, such as ablated tissue areas 235, canbe formed in the tissue during a single procedure performed at one time.

FIG. 7 illustrates in dotted lines an ablated tissue area 335 ofrectangular cross-sectional configuration formed in the tissue S andcontaining six generally circular non-contacting lesions 338 eachsurrounded by unablated tissue. The lesions 338 and ablated tissue area335 are similar to the lesions 38 and ablated tissue area 35 except forthe cross-sectional size of lesions 338 being different from thecross-sectional size of lesions 38. The ablated tissue area 335 willtypically be formed in a single treatment or procedure. The ablatedtissue area 335 can be formed using the ultrasound emitting member 18 byactuating six appropriate transducer elements.

It should be appreciated that the methods of tissue ablation accordingto the present invention can be performed using focused ultrasoundablation devices wherein the transducer elements of the ultrasoundemitting members are not selectively actuatable. For example, FIG. 8illustrates an alternative focused ultrasound ablation device 412 havingfocused ultrasound emitting member 418, which is similar to focusedultrasound emitting member 18 except that focused ultrasound emittingmember 418 includes an array of six transducer elements 428 actuatablesimultaneously or in unison to emit ultrasound energy. The transducerelements 428 are arranged in two rows and three columns and are used toform an ablated tissue area containing six lesions, such as ablatedtissue area 335. Accordingly, it should be appreciated that variousdedicated ultrasound emitting members having different arrays and/ornumbers of transducer elements can be provided, with a particularultrasound emitting member being capable of obtaining a particularablated tissue area of predetermined size, configuration and number oflesions in response to actuation of all of the transducer elements ofthe particular ultrasound emitting member.

FIG. 9 illustrates an alternative, subsurface ablated tissue area 535formed in the tissue S in a manner similar to ablated tissue area 135.However, the ultrasound energy used to form ablated tissue area 535 isof higher intensity and/or is applied to the tissue for a longerduration than the ultrasound energy used to form ablated tissue area135. Accordingly, the lesions 538 of ablated tissue area 535 have agenerally circular surface or cross-sectional configuration larger indiameter than the generally circular cross-sectional configuration oflesions 138 due to greater dispersal of heat from the focusing zones. Asa result, the lesions 538 contact or touch one another but still do notmerge sufficiently to fill the entire ablated tissue area 535 withablated tissue. Although each lesion 538 is not completely surroundedperimetrically by unablated tissue, there is still some unablated tissuewithin the ablated tissue area 535 as shown in FIG. 9 by unablatedtissue disposed between adjacent lesions 538. It should be appreciated,therefore, that the ablated tissue areas formed in accordance with thepresent invention can include a plurality of non-contacting lesions eachcompletely surrounded by unablated tissue and/or a plurality ofcontacting lesions with unablated tissue between the contacting lesions.

In the procedures described and illustrated above, the ultrasoundemitting member is placed against the tissue at a desired location toform an ablated tissue area of final size and configuration in thetissue with focused ultrasound energy generated and emitted by theultrasound emitting member without moving the ultrasound emitting memberfrom the desired location. It should be appreciated, however, that wherethe largest size ablated tissue area capable of being formed in thetissue with the ultrasound emitting member is smaller than the finalsize and/or different from the final configuration desired for theablated tissue area, the ultrasound emitting member can be moved alongto form an ablated tissue area of desired final size and configurationas explained in U.S. patent application Ser. No. 09/487,705.

The methods of the present invention allow tissue ablation to beperformed with minimal trauma and pain for the patient and with fasterhealing and recovery times. By controlling the delivery of ultrasoundenergy to the tissue, the temperature to which the tissue is heated bythe ultrasound energy can be controlled to avoid undesired patientresponses. The ultrasound emitting members can be provided with sensorsfor monitoring the amount of ultrasound energy delivered to the tissueand/or for detecting the temperature to which the tissue is heated,which can be provided as feedback to the controller. The delivery ofultrasound energy to tissue can be controlled to achieve a selectedtemperature, a selected amount of ablation, a desired lesion size or adesired duration of ultrasonic energy delivery. The transducer assemblycan contain ultrasound imaging transducers that can be used to provide areal-time or multiplexed echo feedback on the progress of the ablation,in particular, the changes in mechanical properties of the tissue thatare observed in eco imaging. This imaging can also be used to guide thesteering and focus depth of the transducers energy focus to ensure thatthe desired target tissue is indeed being ablated. Furthermore, theultrasound transducer may sense reflections from the targeted tissuesuch as backscatter echo and spatial compound imaging, etc. to estimatethe thermal dose, tissue temperature and/or necrosis. The ultrasoundemitting members can be disposable or can be designed to be reusable andthusly can be capable of being sterilized to medical standards. Theultrasound emitting members can be provided with disposable covers orguards which can be removed and discarded after use so that theultrasound emitting members can be reused. The transducer or transducerelements can be removable from the ultrasound emitting members allowingdisposability of the ultrasound emitting members and reuse of thetransducer or transducer elements in another ultrasound emitting member.The ultrasound emitting members can be immobilized during use as may beaccomplished with various types of stabilizing members provided on theshafts or on the ultrasound emitting members. The focused ultrasoundablation devices can be provided with imaging capabilities or can beused with various imaging devices as disclosed in U.S. patentapplication Ser. No. 09/487,705. The focused ultrasound ablation devicescan be provided with cooling systems for cooling the ultrasound emittingmembers and/or the transducers as disclosed in U.S. patent applicationSer. No. 09/487,705. The methods of tissue ablation can be performedusing an acoustic coupling medium as disclosed in U.S. patentapplication Ser. No. 09/487,705. A single ultrasound emitting member canbe used to form various different ablated tissue areas of various sizes,configurations, and number of lesions depending on the particulartransducer elements selected for actuation. A plurality of differentultrasound emitting members having non-selectively actuatable transducerelements can be provided with each ultrasound emitting member having adifferent array and/or number of transducer elements to obtain aparticular ablated tissue area of predetermined size, configuration andnumber of lesions when all of the transducer elements of the ultrasoundemitting members are actuated. Any number of ablated tissue areas can beformed with each ablated tissue area surrounded by unablated tissue orwith the ablated tissue areas contiguous to, in abutment with,contacting or overlapping one another to form a single ablated tissuearea. The ultrasound emitting members, the transducers and/or thetransducer elements can be moved relative to the tissue to scan targetareas with focused ultrasound energy, and such scanning can beaccomplished in various diverse ways. The ablated tissue areas caninclude unablated tissue and a plurality of non-contacting lesions, aplurality of contacting lesions or a combination of contacting andnon-contacting lesions. Any number of lesions can be contained in theablated tissue areas including even and odd numbers of lesions.

In one embodiment of the present invention, a hand-held probe having oneor more HIFU transducers may be used to create epicardial lesions, forexample, by dragging the device across the epicardial surface of theheart. In an alternative embodiment of the present invention, atrans-esophageal ablation device having one or more HIFU transducers maybe used to create tissue lesions, for example, by placing the device ina patient's esophagus and ablating cardiac tissue. In anotheralternative embodiment of the present invention, a trans-trachealablation device having one or more HIFU transducers may be used tocreate tissue lesions, for example, by placing the device in a patient'strachea.

FIG. 10 shows diagrammatically a two-dimensional view of the two atriaof a human heart, in which transmural lesions of a Maze procedure areindicated by reference letter C, the undisturbed electrical impulses byA, and the blocked electrical impulses by B. The lesions C are in thenature of scar tissue. One or more lesions C may be formed during anablation procedure. The atria, as viewed epicardially from a loweraspect, include the left atrium 100 and the right atrium 101. Structuralfeatures of the atria include the bases of the pulmonary veins 110, theinferior vena cava 120, the superior vena cava 130, the left atrialappendage 140 and the right atrial appendage 150. A first lesion 160 isa curved lesion that is joined end-to-end such that it encircles thepulmonary veins 110, and is between the pulmonary veins 110 andconductive pathways in the left atrium 100 and between the pulmonaryveins 110 and conductive pathways in the right atrium 101. A secondlesion 165 extends between the superior vena cava 130 and the inferiorvena cava 120 and blocks a first conductive pathway 167. A third lesion170 extends across the left atrium 100 from an intersection 171 with aportion of the first lesion 160 toward the left atrial appendage 140 andblocks a second conductive pathway 172. A fourth lesion 175 extendsalong the right atrium 101 laterally from an intersection 176 with aportion of the second lesion 165 to the annulus of the tricuspid valve(not shown). A fifth lesion 180 extends from an intersection 181 with aportion of the first lesion 160 along the left atrium 100 to the annulusof the mitral valve (not shown) and blocks a third conductive pathway182. A sixth lesion 185 extends along the right atrium 101 toward theright atrial appendage 150. Incisions 142 and 152 correspond to wherethe atrial appendages may be excised. Sutures may be used to close theincisions 142 and 152. Alternatively, incisions 142 and 152, or portionsthereof, may be ablation lesions. One or more of the lesions discussedabove may be created according to one or more embodiments of the presentinvention. For further details regarding the lesion pattern shown inFIG. 10, see U.S. Pat. No. 6,165,174, the disclosure of which isincorporated herein by reference. In addition, U.S. Pat. No. 6,807,968,the disclosure of which is incorporated herein by reference, alsodiscloses the lesion pattern of a Maze ablation procedure.

In one embodiment of the present invention, ablation device 12 may beused to create a right atrial flutter lesion that extends from thetricuspid valve to the coronary sinus. In another embodiment of thepresent invention, ablation device 12 may be used to ablate the SAand/or AV nodes. In another embodiment of the present invention,ablation device 12 may be used to form the Wolf-Parkinson-White ablationprocedure. In another embodiment of the present invention, ablationdevice 12 may be used to isolate the four pulmonary veins by forming asingle lesion encircling of all four veins (as shown in FIG. 10).Alternatively, ablation device 12 may be used to isolate a first pair ofpulmonary veins by forming a lesion encircling two of the four veins. Inaddition, ablation device 12 may be used to isolate the second pair ofpulmonary veins by forming a lesion encircling the remaining two veins.The two encircling lesions may then be connected with a connectinglesion placed in between the two lesions, which connect the twoencircling lesions together. In another embodiment of the presentinvention, ablation device 12 may be used to isolate each pulmonary veinindividually by forming four separate lesions encircling each of thefour veins. Connecting lesions may also be formed connecting the fourseparate lesions together, if desired.

FIG. 11 shows a schematic view of one embodiment of a system 900 forablating tissue while positioning, manipulating, holding, grasping,immobilizing and/or stabilizing tissue in accordance with the presentinvention. In this embodiment, system 900 is shown to comprisetissue-engaging device 200, a suction source 300, a fluid source 400, aHIFU ablation assembly 10, a sensor 600 and an imaging device 800. TheHIFU ablation assembly 10 includes a focused ultrasound ablation orstimulation device 12, a power supply 14 and a controller 16. System 900may also include a drug delivery device, a guidance device and/or anerve and/or cardiac stimulation device (all not shown in FIG. 11). Thetissue-engaging device may comprise one or more suction or vacuum ports,openings, orifices, channels or elements positioned on, along, within oradjacent a tissue contact surface. The suction ports, openings,orifices, channels or elements may communicate suction through thetissue contact surface to the atmosphere to engage or grasp tissue viasuction. The drug delivery device may be used to deliver drugs and/orbiological agents to a patient. The imaging device may be used toilluminate a surgical site. The imaging and guidance devices may be usedto help control and guide the HIFU device.

In one embodiment of the present invention, the tissue-engaging devicemay comprise one or more mechanical means for engaging and/or graspingtissue. For example, the tissue-engaging head may comprise one or morehooks, clamps, screws, barbs, sutures, straps, tethers and/or staples.The tissue-engaging device may comprise a cuff or basket-type devicedesigned to fit completely or partially around an organ, e.g., a heart.The tissue-engaging device may comprise one or more chemical means forengaging and/or grasping tissue. For example, the tissue-engaging devicemay comprise tissue glue or adhesive. The tissue-engaging device maycomprise one or more coupling means for engaging and/or grasping tissue.For example, a suction means in addition to a mechanical means may beused to engage or grasp tissue. A magnetic means may also be used toengage or grasp tissue.

In one embodiment of the present invention, the tissue-engaging devicemay include a sufficiently resiliently flexible head that may be flexedto allow it to be pushed through a small incision, cannula or port. Onceinside the chest cavity, the flexible head will return to its originalshape. For example, the head may be configured to be collapsable forentering into a thoracic cavity through a small incision, cannula orport in endoscopic and/or closed chest surgery. In addition, to closedchest surgery, this invention is applicable to open chest/split sternumsurgery, in particular open chest, beating heart surgery forrepositioning the heart to improve access to various locations of theheart.

The tissue-engaging device may include one or more fluid openings fordelivery and/or removal of one or more fluids. The tissue-engagingdevice may include needles for injection of fluids, drugs and/or cellsinto organ tissue. The tissue-engaging device may comprise a catheter orcannula for blood removal or delivery into an organ, e.g., a heart. Inthe case of the heart, the cannula or catheter may be placed through thewall of the heart and into an interior chamber of the heart comprisingblood, for example, into the left ventricle. Blood may be removed ordelivered via a blood pump. For example, a catheter or cannula of thetissue-engaging device may be attached to a CPB circuit or a cardiacassist circuit such as an LVAD circuit. The tissue-engaging device mayinclude one or more openings for delivery or removal of one or moregases including smoke evacuation.

One or more parts or portions of the tissue-engaging device may bedesigned to be implantable. For example, following an ablationprocedure, a head portion of the tissue-engaging device may be leftwithin the patient, thereby providing benefit to the patient. Thetissue-engaging head may be made of one or more biodegradable materials,thereby allowing the head to be absorbed by the patient over time.

The tissue-engaging device may comprise a maneuvering or supportapparatus or means such as a shaft, a handle or an arm connected to atissue-engaging head to position the head to thereby position or holdtissue such as the heart. The tissue-engaging head of thetissue-engaging device may be rigidly, permanently, moveably, orremoveably coupled, connected or mounted onto the maneuvering or supportapparatus or means. The support shaft, handle or arm may be rigid,flexible, telescoping or articulating. The shaft, handle or arm maycomprise one or more hinges or joints for maneuvering and placing thedevice against tissue. The hinges or joints of the maneuvering orsupport apparatus may be actuated remotely, for example with pull wires,from outside a patient's body. The shaft, handle or arm may be malleableor shapeable. The maneuvering or support means may be made of a shapememory alloy wherein heat may be use to change the shape of themaneuvering or supporting means.

In one method of the present invention, the medical procedure mayinclude the use of a tissue-engaging device as described, for example,in U.S. patent application Ser. No. 10/643,299, U.S. Patent ApplicationPublication No. 2004/0138522 and U.S. Pat. No. 6,447,443, thedisclosures of which are incorporated herein by reference, incombination with one or more focused ultrasound ablation devices. Thecombination of one or more tissue-engaging devices and one or moretissue ablation devices may be used to position and ablate tissue, e.g.,endocardial, myocardial and/or epicardial tissue of the heart, locatedwithin a body cavity, e.g., the thoracic cavity. Other body organtissue, such as the liver, lungs or kidney, may also be positioned andablated. An ablation procedure that utilizes a tissue-engaging devicemay be an open chest procedure, a closed chest procedure, a minimallyinvasive procedure, a beating heart procedure, and/or a stopped heartprocedure. The tissue-engaging device may be positioned and used, forexample, through a sternotomy, through a thoracotomy that avoids thesternal splitting incision of conventional cardiac surgery, through amini-thoracotomy, through a sub-xyphoid incision, percutaneously,transvenously, arthroscopically, endoscopically, for example, through apercutaneous port, through a stab wound or puncture, through a small orlarge incision, for example, in the chest, in the groin, in the abdomen,in the neck or in the knee, or in combinations thereof. Thetissue-engaging device may be guided into a desired position usingvarious imaging and/or guidance techniques, e.g., fluoroscopic guidancetechniques.

Tissue-engaging device 200 may be used to grasp and position thepericardium away from the surface of the heart thereby creating spacebetween the surface of the heart and the pericardium. This type ofprocedure may be termed “tenting”. Tissue-engaging device 200 may beused to grasp and position a heart away from a rib cage, for example inan endoscopic procedure, thereby creating space for a surgeon to workbetween the heart and the rib cage. Tissue-engaging device 200 may beused to grasp and position a heart away from other adjacent or nearbyorgans thereby creating space for a surgeon to work.

An endoscope or thoracoscope may be used to view on or more aspects ofthe medical procedure. Incisions may be maintained open by insertion ofa cannula or port through the incision so that instruments, such as atissue-engaging device and/or HIFU ablation device, can be advancedthrough the lumen of the cannula or port. If a trocar is used, a trocarrod is inserted into the trocar sleeve, and the sharpened tip of thetrocar rod is advanced to puncture the abdomen or chest to create theincision into the thoracic cavity. The trocar rod is then withdrawnleaving the trocar sleeve in place so that one or more surgicalinstruments may be inserted into the thoracic cavity through the trocarsleeve lumen.

In one embodiment of the invention, the surgeon may decide to stop theheart. For example, a series of catheters may be used to stop blood flowthrough the aorta and to administer cardioplegia solution. A closedchest, stopped heart procedure may utilize groin cannulation toestablish cardiopulmonary bypass (CPB) and an intra-aortic ballooncatheter that functions as an internal aortic clamp by means of anexpandable balloon at its distal end used to occlude blood flow in theascending aorta. A full description of one example of an endoscopictechnique is found in U.S. Pat. No. 5,452,733, the disclosure of whichis incorporated herein by reference.

The tissue-engaging device may be used to position, manipulate, hold,grasp, immobilize and/or stabilize an area of tissue and/or an organ,such as a heart, during an ablation procedure. For example, thetissue-engaging device may be used to engage an area of tissue, such asan organ, and position the area of tissue or organ into anon-physiological orientation. For example, the tissue-engaging device200, shown in FIG. 12, is shown being used in an open chest, sternotomyprocedure to position the heart into a non-physiological orientation,thereby creating access to areas of the heart that an ablation devicepositioned, for example, through the chest opening or sternotomy wouldnot have had ablative access to prior to positioning of the heart. FIG.12 shows tissue-engaging device 200 locked onto a sternal retractor 250fixed to a patient's chest. In FIG. 12, tissue-engaging device 200 isshown supporting a patient's heart 205 while it is engaged or attachedto the apex of the patient's heart. The patient's heart may be beatingor stopped. As shown in FIG. 13, a hand-held ablation device 12positioned through a sternotomy and having at least one HIFU transducermay be used to create one or more epicardial lesions, for example, bymoving or dragging the device across the epicardial surface of theheart. As shown in FIG. 13, the one or more epicardial lesions may bemade while the heart is positioned in a non-physiological orientation.

The tissue-engaging device 200, shown in FIG. 14, is shown being used ina closed chest, non-sternotomy procedure to position the heart 205 intoa non-physiological orientation. Positioning the heart in anon-physiological can create access to areas of the heart that anablation device positioned, for example, through a thoracotomy or port,through the patient's esophagus or trachea, or positioned outside thechest would not have had ablative access to prior to positioning of theheart.

In one method of the present invention, a focused ultrasound ablationdevice 12 is placed within the trachea and/or bronchi of the lungs toablate tissue within the thoracic cavity of a patient. The ultrasoundablation device is sized and shaped to fit within the trachea and/orbronchi of the lungs. Shaft 20 may be of a sufficient length to allowinsertion of an appropriately sized ultrasound emitting member 18 intothe trachea and/or bronchi of the lungs of a patient through thepatient's oral cavity. Once placed in the desired position, ultrasoundenergy may be focused through the wall of the trachea or bronchi andinto tissue to be ablated. To ablate tissue not positioned within thefocusing range of the ultrasound ablation device, a tissue-engagingdevice, as described earlier, may be used to move and position tissue ofinterest within the focusing range of the ablation device. Thetissue-engaging device may be used to position tissue prior to anablation procedure, during an ablation procedure and/or following anablation procedure. A variety of tissue types and/or organs may beablated or treated by one or more ultrasound ablations device placedwithin the trachea and/or bronchi of the lungs. Alternatively, a varietyof tissue types and/or organs may be ablated or treated by one or moreultrasound ablation devices positioned through one or more other bodycavity openings of the patient and/or positioned on the skin of thepatient. For example, one or more ultrasound ablation devices may bepositioned through the mouth, the nose, the anus, the urethra and/or thevagina. The ablation procedure may include one or more imaging methodsor devices.

In one method of the present invention, see FIG. 15, a focusedultrasound ablation device 12 is placed within the esophagus 210 toablate tissue of the heart 205, for example, in a Maze procedure. Theultrasound ablation device may be sized and shaped to fit within theesophagus 210. Shaft 20 may be of a sufficient length to allow insertionof an appropriately sized ultrasound emitting member 18 into theesophagus of a patient through the patient's oral cavity. Once placed inthe desired position, ultrasound energy may be focused through the wallof the esophagus and into cardiac tissue to be ablated. Cardiac tissueis then ablated. To ablate cardiac tissue not positioned within thefocusing range of the ultrasound ablation device, a tissue-engagingdevice 200, as described earlier, may be used to move and position theheart to move tissue of interest within the focusing range of theablation device. The tissue-engaging device 200 may be used to positiontissue prior to an ablation procedure, during an ablation procedureand/or following an ablation procedure. In addition to cardiac tissue,other tissue types and/or organs may be ablated or treated by one ormore ultrasound ablation devices placed within the esophagus of thepatient.

In one embodiment of the invention, ablation device 12 may comprise, forexample, one or more inflatable and/or compressible members, which maybe inflated or decompressed with air or liquid, for example, while thedevice is positioned within a body cavity to press the surface of theablating member 18 firmly against the body cavity wall. For example,device 12 may comprise a balloon, which may be inflated with air orliquid while the device is positioned within the esophagus, the tracheaand/or bronchi of the lungs to press the surface of the ablating member18 firmly against the body cavity wall.

In one method of the present invention, an imaging device 800 may beused to image tissue such as heart tissue as shown in FIG. 16. Theimaging device may be appropriately sized to allow its placement withinthe esophagus of the patient. Alternatively, the imaging device may beappropriately sized to allow its placement within the trachea and/orbronchi of the lungs of the patient. Alternatively, one or more imagingdevices may be positioned through one or more other body cavity openingsof the patient and/or positioned on the skin of the patient. Forexample, one or more imaging devices may be positioned through themouth, the nose, the anus, the urethra and/or the vagina. In oneembodiment of the present invention, ablation system 10 may include oneor more imaging capabilities. For example, ultrasound imagingcapabilities may be incorporated into ultrasound ablation device 12 sothat a single device could be used to both image and ablate tissue. Onceplaced in the desired position, for example in the esophagus, ultrasoundenergy may be focused through the wall of the esophagus and into cardiactissue to be imaged. Cardiac tissue is then imaged and the location oftissue to be ablated is determined. To image cardiac tissue notpositioned within the focusing range of the imaging device, atissue-engaging device 200, as described earlier, may be used to moveand position the tissue of interest within the focusing range of theimaging device. The tissue-engaging device 200 may be used to positiontissue prior to an imaging procedure, during an imaging procedure and/orfollowing an imaging procedure. In addition to cardiac tissue, othertissue types and/or organs may be positioned and imaged by one or morepositioning and imaging devices. In one embodiment of the presentinvention, the positioning or tissue-engaging device may comprise one ormore imaging capabilities, e.g., ultrasound imaging.

In one embodiment of the present invention, a nerve stimulatorcomprising one or more nerve stimulation electrodes may be used tostimulate the patient's vagal nerve to slow or stop the patient's heartduring an ablation procedure. The patient may be given one or more drugsto help stop the beating of the heart and/or to prevent “escape” beats.Following vagal stimulation, the heart may be allowed to return to itsusual cardiac rhythm. Alternatively, the heart may be paced, therebymaintaining a normal cardiac output. Vagal stimulation, alone or incombination with electrical pacing and/or drugs, may be used selectivelyand intermittently to allow a surgeon to perform an ablation procedureon a temporarily stopped heart. For example, stimulation of the vagusnerve in order to temporarily and intermittently slow or stop the heartis described in U.S. Pat. No. 6,006,134, No. 6,449,507, No. 6,532,388,No. 6,735,471, No. 6,718,208, No. 6,228,987, No. 6,266,564, No.6,487,446 and U.S. patent application Ser. No. 09/670,370 filed Sep. 26,2000, Ser. No. 09/669,961 filed Sep. 26, 2000, Ser. No. 09/670,440 filedSep. 26, 2000. These patents and patent applications are incorporatedherein by reference in their entireties.

Electrodes used to stimulate a nerve such as the vagal nerve may be, forexample, non-invasive, e.g., clips, or invasive, e.g., needles orprobes. The application of an electrical stimulus to the right or leftvagal nerve may include, but is not limited to bipolar and/or monopolartechniques. Different electrode positions are accessible through variousaccess openings, for example, in the cervical or thorax regions. Nervestimulation electrodes may be positioned through a thoracotomy,sternotomy, endoscopically through a percutaneous port, through a stabwound or puncture, through a small incision in the neck or chest,through the internal jugular vein, the esophagus, the trachea, placed onthe skin or in combinations thereof. Electrical stimulation may becarried out on the right vagal nerve, the left vagal nerve or to bothnerves simultaneously or sequentially. The present invention may includevarious electrodes, catheters and electrode catheters suitable for vagalnerve stimulation to temporarily stop or slow the beating heart alone orin combination with other heart rate inhibiting agents.

Nerve stimulation electrodes may be endotracheal, endoesophageal,intravascular, transcutaneous, intracutaneous, patch-type, balloon-type,cuff-type, basket-type, umbrella-type, tape-type, screw-type, barb-type,metal, wire or suction-type electrodes. Guided or steerable catheterdevices comprising electrodes may be used alone or in combination withthe nerve stimulation electrodes. For example, a catheter comprising oneor more wire, metal strips or metal foil electrodes or electrode arraysmay be inserted into the internal jugular vein to make electricalcontact with the wall of the internal jugular vein, and thus stimulatethe vagal nerve adjacent to the internal jugular vein. Access to theinternal jugular vein may be via, for example, the right atrium, theright atrial appendage, the inferior vena cava or the superior venacava. The catheter may comprise, for example, a balloon, which may beinflated with air or liquid to press the electrodes firmly against thevessel wall. Similar techniques may be performed by insertion of acatheter-type device into the trachea or esophagus. Additionally,tracheal devices, e.g., tracheal tubes, tracheal ablation devices,tracheal imaging devices, and/or esophageal devices, e.g., esophagealtubes, esophageal ablation devices, esophageal imaging devices,comprising electrodes may be used.

Nerve stimulation electrodes may be oriented in any fashion along thecatheter device, including longitudinally or transversely. Variousimaging techniques or modalities, as discussed earlier, such asultrasound, fluoroscopy and echocardiography may be used to facilitatepositioning of the electrodes. If desired or necessary, avoidance ofobstruction of air flow or blood flow may be achieved with notchedcatheter designs or with catheters, which incorporate one or moretunnels or passageways.

In one embodiment of the present invention, the location of theelectrodes is chosen to elicit maximum bradycardia effectiveness whileminimizing current spread to adjacent tissues and vessels and to preventthe induction of post stimulation tachycardia. Furthermore, anon-conductive material such as plastic may be employed to sufficientlyenclose the electrodes of all the configurations to shield them from thesurrounding tissues and vessels, while exposing their confronting edgesand surfaces for positive contact with the vagal nerve or selectedtissues.

FIG. 17 shows a flow diagram of one embodiment of the present invention.The patient is prepared for a medical procedure at 700. Once the patientis prepared, the heart is engaged and positioned using tissue-engagingdevice 200 (Block 705). Once the heart is positioned in a desiredorientation, e.g., a non-physiological orientation, a nerve thatcontrols the beating of the heart is stimulated to slow down or stop thecontractions of the heart (Block 708). Such a nerve may be for example avagal nerve. During this time, one or more of a variety ofpharmacological agents or drugs may be delivered to the patient. Drugsmay be administered without nerve stimulation. The types of drugsadministered may produce reversible asystole of a heart whilemaintaining the ability of the heart to be electrically paced. Otherdrugs may be administered for a variety of functions and purposes. Drugsmay be administered at the beginning of the procedure, intermittentlyduring the procedure, continuously during the procedure or following theprocedure. Examples of one or more drugs that may be administeredinclude a beta-blocker, a cholinergic agent, a cholinesterase inhibitor,a calcium channel blocker, a sodium channel blocker, a potassium channelagent, adenosine, an adenosine receptor agonist, an adenosine deaminaseinhibitor, dipyridamole, a monoamine oxidase inhibitor, digoxin,digitalis, lignocaine, a bradykinin agent, a serotoninergic agonist, anantiarrythmic agent, a cardiac glycoside, a local anesthetic, atropine,a calcium solution, an agent that promotes heart rate, an agent thatpromotes heart contractions, dopamine, a catecholamine, an inotropeglucagon, a hormone, forskolin, epinephrine, norepinephrine, thyroidhormone, a phosphodiesterase inhibitor, prostacyclin, prostaglandin anda methylxanthine.

Typically, vagal nerve stimulation prevents the heart from contracting.This non-contraction must then be followed by periods without vagalnerve stimulation during which the heart is allowed to contract, andblood flow is restored throughout the body. Following initial slowing orstopping of the heart, a medical procedure, such as imaging and/orablation, is begun (Block 710). In one embodiment of the invention, oneor more ultrasound ablation devices are positioned within the trachea,bronchi of the lungs and/or esophagus of the patient and ultrasoundenergy is emitted from the one or more ablation devices and is focusedwithin tissue, e.g., cardiac tissue. Alternatively, an ablation devicemay be placed on the patient, e.g., on the chest of the patient.Following a brief interval of nerve stimulation while the ablationprocedure is performed, nerve stimulation is ceased (Block 713) and theheart is allowed to contract.

The heart may be free to beat on its own or a cardiac stimulator orpacemaker comprising one or more cardiac stimulation electrodes may beused to cause the heart to contract (Blocks 722 and 724). Cardiacstimulation electrodes used to stimulate the heart may be, for example,non-invasive, e.g., clips, or invasive, e.g., needles or probes. Cardiacelectrodes may be positioned through a thoracotomy, sternotomy,endoscopically through a percutaneous port, through a stab wound orpuncture, through a small incision in the chest, placed on the chest orin combinations thereof. The present invention may also use variouselectrodes, catheters and electrode catheters suitable for pacing theheart, e.g., epicardial, patch-type, intravascular, balloon-type,basket-type, umbrella-type, tape-type electrodes, suction-type, pacingelectrodes, endotracheal electrodes, endoesophageal electrodes,transcutaneous electrodes, intracutaneous electrodes, screw-typeelectrodes, barb-type electrodes, bipolar electrodes, monopolarelectrodes, metal electrodes, wire electrodes and cuff electrodes.Guided or steerable catheter devices comprising electrodes may be usedalone or in combination with the electrodes. One or more cardiacelectrodes, e.g., stimulation and/or monitoring electrodes, may bepositioned on tissue-engaging device 200.

If the ablation procedure needs to continue or a new ablation procedureis to be performed, the heart again may be slowed or stopped via vagalnerve stimulation. In addition, the heart may be repositioned ifnecessary or desired at Block 748.

In one embodiment of the present invention, a probe device sized andshaped to fit within the trachea, bronchi and/or esophagus of thepatient may comprise one or more nerve stimulation electrodes, membersor elements and one or more ultrasound ablation members or elements. Theprobe device may be positioned within the trachea, bronchi and/oresophagus of the patient. The nerve stimulation electrodes may be usedto stimulate one or more nerves of the patient, e.g., a vagal nerve, asdisclosed earlier, while the probe device is positioned within thetrachea, bronchi and/or esophagus of the patient. The ultrasoundablation members may be used to emit ultrasound energy to ablate tissue,e.g., cardiac tissue, as disclosed earlier, while the probe device ispositioned within the trachea, bronchi and/or esophagus of the patient.The nerve stimulation electrodes may be coupled to a nerve stimulator,e.g., used to stimulate the patient's vagal nerve to slow or stop thepatient's heart during an ablation procedure.

In one embodiment of the present invention, the tissue-engaging devicemay include one or more ultrasound ablation elements, as describedearlier. The tissue-engaging device comprising one or more ultrasoundablation elements may be used to move and position tissue, e.g., hearttissue, as well as to ablate tissue within the focusing range of the oneor more ultrasound ablation elements. The tissue-engaging device may beused to position tissue prior to an ablation procedure, during anablation procedure and/or following an ablation procedure. In additionto cardiac tissue, other tissue types and/or organs may be ablated ortreated by one or more ultrasound ablation elements of the device.

The distal end of the tissue-engaging device may be positioned within apatient through an incision, a stab wound, a port, a sternotomy and/or athoracotomy. An endoscope may be used to help position thetissue-engaging device.

In one embodiment of the present invention, the ultrasound ablationdevice or system may comprise one or more switches to facilitate itsregulation by a physician or surgeon. One example of such a switch is afoot pedal. The switch may also be, for example, a hand switch, or avoice-activated switch comprising voice-recognition technologies. Theswitch may be incorporated in or on one of the surgeon's instruments,such as surgical site retractor, or any other location easily andquickly accessed by the surgeon.

The ultrasound ablation device or system may include a display and/orother means of indicating the status of various components of the deviceto the surgeon such as a numerical display, gauges, a monitor display oraudio feedback. The ultrasound ablation device may also include one ormore visual and/or audible signals used to prepare a surgeon for thestart or stop of the ablation procedure. Controller 16 may synchronizedelivery of ablation energy to the ablation device 12 between heartbeats to reduce inadvertent tissue damage. Controller 16 may be slavedto a nerve stimulator and/or a cardiac stimulator. Alternatively, anerve stimulator and/or cardiac stimulator may be slaved to controller16. Alternatively, controller 16 may be capable of nerve stimulationand/or cardiac stimulation.

In one embodiment of the present invention, one or more diagnostictransducers may be used to measure the desired ablative tissue area.System 900 would then suggest and/or control a specific transducer basedon the desired lesion depth and configuration. The system could thendeliver the amount and type of energy required to create the desiredlesion. Electrodes of system 900 may be used for cardiac pacing,defibrillation, cardioversion, sensing, stimulation, and/or mapping.

System 900 may include suction source 300 for providing suction totissue-engaging device 200 and/or ablation device 12. Tissue-engagingdevice 200 and/or ablation device 12 may be attached to a flexible orrigid hose or tubing for supplying suction and/or fluids from a suitablesuction source and/or fluid source to the target tissue surface throughsuction and/or fluid elements, openings, orifices, or ports of device200 and/or device 12. The hose or tubing may comprise one or morestopcocks and/or connectors such as luer connectors. Suction may beprovided to device 200 and/or device 12 by the standard suctionavailable in the operating room. Suction source 300 may be coupled totissue-engaging device 200 and/or device 12 with a buffer flask and/orfilter. Suction may be provided at a negative pressure of between200-600 mm Hg with 400 mm Hg preferred. As used herein, the terms“vacuum” or “suction” refer to negative pressure relative to atmosphericor environmental air pressure in the operating room.

Suction may be provided via one or more manual or electric pumps,syringes, suction or squeeze bulbs or other suction or vacuum producingmeans, devices or systems. Suction source 300 may comprise one or morevacuum regulators, resistors, stopcocks, connectors, valves, e.g.,vacuum releasing valves, filters, conduits, lines, tubes and/or hoses.The conduits, lines, tubes, or hoses may be flexible or rigid. Forexample, a flexible suction line may be used to communicate suction todevice 200 and/or device 12, thereby allowing device 200 and/or device12 to be easily manipulated by a surgeon. Another method that wouldallow the surgeon to easily manipulate device 200 and/or device 12includes incorporation of suction source 300 into device 200 and/ordevice 12. For example, a small battery operated vacuum pump or squeezebulb may be incorporated into device 200 and/or device 12.

Suction source 300 may be slaved to ablation assembly 10,tissue-engaging device 200, fluid source 400, sensor 600, imaging device800, a drug delivery device, a guidance device and/or a stimulationdevice. For example, suction source 300 may be designed to automaticallystop suction when controller 16 sends a signal to stop suction. Suctionsource 300 may include a visual and/or audible signal used to alert asurgeon to any change in suction. For example, a beeping tone orflashing light may be used to alert the surgeon when suction is present.Suction source 300 may be slaved to a robotic system or a robotic systemmay be slaved to suction source 300. Suction may be used to secure,anchor or fix tissue-engaging device 200 and/or device 12 to an area oftissue. The area of tissue may comprise a beating heart or a stoppedheart. Suction may be used to remove or aspirate fluids from the targettissue site. Fluids removed may include, for example, blood, saline,Ringer's solution, ionic fluids, contrast fluids, irrigating fluids andenergy-conducting fluids. Steam, vapor, smoke, gases and chemicals mayalso be removed via suction.

System 900 may include fluid source 400 for providing fluids, forexample, to tissue-engaging device 200, ablation device 12 and/or thepatient. Tissue-engaging device 200 may be attached to a flexible orrigid hose or tubing for supplying fluids from fluid source 400 to thetarget tissue through fluid elements, openings, orifices, or ports ofdevice 200. Ablation device 12 may be attached to a flexible or rigidhose or tubing for receiving fluids from fluid source 400 and forsupplying fluids, if desired, to the target tissue through fluidelements, openings, orifices, or ports of device 12.

Fluid source 400 may be any suitable source of fluid. Fluid source 400may include a manual or electric pump, an infusion pump, a peristalticpump, a roller pump, a centrifugal pump, a syringe pump, a syringe, orsqueeze bulb or other fluid moving means, device or system. For example,a pump may be connected to a shared power source or it may have its ownsource of power. Fluid source 400 may be powered by AC current, DCcurrent, or it may be battery powered either by a disposable orre-chargeable battery. Fluid source 400 may comprise one or more fluidregulators, e.g., to control flow rate, valves, fluid reservoirs,resistors, filters, conduits, lines, tubes and/or hoses. The conduits,lines, tubes, or hoses may be flexible or rigid. For example, a flexibleline may be connected to devices 12 and/or 200 to deliver fluid and/orremove fluid, thereby allowing device 200 to be easily manipulated by asurgeon. Fluid reservoirs may include an IV bag or bottle, for example.

Fluid source 400 may be incorporated into tissue-engaging device 200and/or ablation device 12, thereby delivering fluid or removing fluid atthe target tissue site. Fluid source 400 may be slaved totissue-engaging device 200 and/or ablation device 12, suction source300, sensor 600 and/or imaging device 800. For example, fluid source 400may be designed to automatically stop or start the delivery of fluidwhile tissue-engaging device 200 is engaged with tissue or whileablation device 12 is ablating tissue. Ablation system 10,tissue-engaging device 200, suction source 300, fluid source 400, sensor600 and/or imaging device 800 may be slaved to a robotic system or arobotic system may be slaved to ablation system 10, tissue-engagingdevice 200, suction source 300, fluid source 400, sensor 600 and/orimaging device 800.

Fluid source 400 may comprise one or more switches, e.g., asurgeon-controlled switch. One or more switches may be incorporated inor on fluid source 400 or any other location easily and quickly accessedby the surgeon for regulation of fluid delivery by the surgeon. A switchmay be, for example, a hand switch, a foot switch, or a voice-activatedswitch comprising voice-recognition technologies. A switch may bephysically wired to fluid source 400 or it may be a remote controlswitch. Fluid source 400 and/or system 10 may include a visual and/oraudible signal used to alert a surgeon to any change in the delivery offluid. For example, a beeping tone or flashing light may be used toalert the surgeon that a change has occurred in the delivery of fluid.

Fluids delivered to tissue-engaging device 200 and/or ablation device 12may include saline, e.g., normal, hypotonic or hypertonic saline,Ringer's solution, ionic, contrast, blood, and/or energy-conductingliquids. An ionic fluid may electrically couple an electrode to tissuethereby lowering the impedance at the target tissue site. An ionicirrigating fluid may create a larger effective electrode surface. Anirrigating fluid may cool the surface of tissue thereby preventing overheating or cooking of tissue which can cause popping, desiccation, andcharring of tissue. A hypotonic irrigating fluid may be used toelectrically insulate a region of tissue. Fluids delivered totissue-engaging device 200 and/or ablation device 12 may include gases,adhesive agents and/or release agents.

Diagnostic or therapeutic agents, such as one or more radioactivematerials and/or biological agents such as, for example, ananticoagulant agent, an antithrombotic agent, a clotting agent, aplatelet agent, an anti-inflammatory agent, an antibody, an antigen, animmunoglobulin, a defense agent, an enzyme, a hormone, a growth factor,a neurotransmitter, a cytokine, a blood agent, a regulatory agent, atransport agent, a fibrous agent, a protein, a peptide, a proteoglycan,a toxin, an antibiotic agent, an antibacterial agent, an antimicrobialagent, a bacterial agent or component, hyaluronic acid, apolysaccharide, a carbohydrate, a fatty acid, a catalyst, a drug, avitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, anantiviral agent, a viral agent or component, a genetic agent, a ligandand a dye (which acts as a biological ligand) may be delivered with orwithout a fluid to the patient. Biological agents may be found in nature(naturally occurring) or may be chemically synthesized. Cells and cellcomponents, e.g., mammalian and/or bacterial cells, may be delivered tothe patient. A platelet gel or tissue adhesive may be delivered to thepatient.

One or more of a variety of pharmacological agents, biological agentsand/or drugs may be delivered or administered to a patient, for avariety of functions and purposes as described below, prior to a medicalprocedure, intermittently during a medical procedure, continuouslyduring a medical procedure and/or following a medical procedure. Forexample, one or more of a variety of pharmacological agents, biologicalagents and/or drugs, as discussed above and below, may be deliveredbefore, with or after the delivery of a fluid.

Drugs, drug formulations or compositions suitable for administration toa patient may include a pharmaceutically acceptable carrier or solutionin an appropriate dosage. There are a number of pharmaceuticallyacceptable carriers that may be used for delivery of various drugs, forexample, via direct injection, oral delivery, suppository delivery,transdermal delivery, epicardial delivery and/or inhalation delivery.Pharmaceutically acceptable carriers include a number of solutions,preferably sterile, for example, water, saline, Ringer's solution and/orsugar solutions such as dextrose in water or saline. Other possiblecarriers that may be used include sodium citrate, citric acid, aminoacids, lactate, mannitol, maltose, glycerol, sucrose, ammonium chloride,sodium chloride, potassium chloride, calcium chloride, sodium lactate,and/or sodium bicarbonate. Carrier solutions may or may not be buffered.

Drug formulations or compositions may include antioxidants orpreservatives such as ascorbic acid. They may also be in apharmaceutically acceptable form for parenteral administration, forexample to the cardiovascular system, or directly to the heart, such asintracoronary infusion or injection. Drug formulations or compositionsmay comprise agents that provide a synergistic effect when administeredtogether. A synergistic effect between two or more drugs or agents mayreduce the amount that normally is required for therapeutic delivery ofan individual drug or agent. Two or more drugs may be administered, forexample, sequentially or simultaneously. Drugs may be administered viaone or more bolus injections and/or infusions or combinations thereof.The injections and/or infusions may be continuous or intermittent. Drugsmay be administered, for example, systemically or locally, for example,to the heart, to a coronary artery and/or vein, to a pulmonary arteryand/or vein, to the right atrium and/or ventricle, to the left atriumand/or ventricle, to the aorta, to the AV node, to the SA node, to anerve and/or to the coronary sinus. Drugs may be administered ordelivered via intravenous, intracoronary and/or intraventricularadministration in a suitable carrier. Examples of arteries that may beused to deliver drugs to the AV node include the AV node artery, theright coronary artery, the right descending coronary artery, the leftcoronary artery, the left anterior descending coronary artery andKugel's artery. Drugs may be delivered systemically, for example, viaoral, transdermal, intranasal, suppository or inhalation methods. Drugsalso may be delivered via a pill, a spray, a cream, an ointment or amedicament formulation.

In one embodiment of the present invention, system 900 may include adrug delivery device (not shown). The drug delivery device may comprisea catheter, such as a drug delivery catheter or a guide catheter, apatch, such as a transepicardial patch that slowly releases drugsdirectly into the myocardium, a cannula, a pump and/or a hypodermicneedle and syringe assembly. A drug delivery catheter may include anexpandable member, e.g., a low-pressure balloon, and a shaft having adistal portion, wherein the expandable member is disposed along thedistal portion. A catheter for drug delivery may comprise one or morelumens and may be delivered endovascularly via insertion into a bloodvessel, e.g., an artery such as a femoral, radial, subclavian orcoronary artery. The catheter can be guided into a desired positionusing various guidance techniques, e.g., flouroscopic guidance and/or aguiding catheter or guide wire techniques. Drugs may be delivered via aniontophoretic drug delivery device placed on the heart. In general, thedelivery of ionized drugs may be enhanced via a small current appliedacross two electrodes. Positive ions may be introduced into the tissuesfrom the positive pole, or negative ions from the negative pole. The useof iontophoresis may markedly facilitate the transport of certainionized drug molecules. For example, lidocaine hydrochloride may beapplied to the heart via a drug patch comprising the drug. A positiveelectrode could be placed over the patch and current passed. Thenegative electrode would contact the heart or other body part at somedesired distance point to complete the circuit. One or more of theiontophoresis electrodes may also be used as nerve stimulationelectrodes or as cardiac stimulation electrodes.

A drug delivery device may be incorporated into tissue-engaging device200 and/or ablation device 12, thereby delivering drugs at or adjacentthe target tissue site or the drug delivery device may be placed or usedat a location differing from the location of tissue-engaging device 200and/or ablation device 12. For example, a drug delivery device may beplaced in contact with the inside surface of a patient's heart whiletissue-engaging device 200 and/or ablation device 12 is placed or usedon the outside surface of the patient's heart.

The drug delivery device may be slaved to ablation system 10,tissue-engaging device 200, suction source 300, fluid source 400, sensor60 and/or imaging device 800. For example, a drug delivery device may bedesigned to automatically stop or start the delivery of drugs duringtissue engagement of tissue-engaging device 200 and/or during tissueablation via ablation device 12. The drug delivery device may be slavedto a robotic system or a robotic system may be slaved to the drugdelivery device.

The drug delivery device may comprise one or more switches, e.g., asurgeon-controlled switch. One or more switches may be incorporated inor on the drug delivery device or any other location easily and quicklyaccessed by the surgeon for regulation of drug delivery by the surgeon.A switch may be, for example, a hand switch, a foot switch, or avoice-activated switch comprising voice-recognition technologies. Aswitch may be physically wired to the drug delivery device or it may bea remote control switch. The drug delivery device and/or system 900 mayinclude a visual and/or audible signal used to alert a surgeon to anychange in the medical procedure, e.g., in the delivery of drugs. Forexample, a beeping tone or flashing light that increases in frequency asthe rate of drug delivery increases may be used to alert the surgeon.

The two divisions of the autonomic nervous system that regulate theheart have opposite functions. First, the adrenergic or sympatheticnervous system increases heart rate by releasing epinephrine andnorepinephrine. Second, the parasympathetic system also known as thecholinergic nervous system or the vagal nervous system decreases heartrate by releasing acetylcholine. Catecholamines such as norepinephrine(also called noradrenaline) and epinephrine (also called adrenaline) areagonists for beta-adrenergic receptors. An agonist is a stimulantbiomolecule or agent that binds to a receptor.

Beta-adrenergic receptor blocking agents compete with beta-adrenergicreceptor stimulating agents for available beta-receptor sites. Whenaccess to beta-receptor sites are blocked by receptor blocking agents,also known as beta-adrenergic blockade, the chronotropic or heart rate,inotropic or contractility, and vasodilator responses to receptorstimulating agents are decreased proportionately. Therefore,beta-adrenergic receptor blocking agents are agents that are capable ofblocking beta-adrenergic receptor sites.

Since beta-adrenergic receptors are concerned with contractility andheart rate, stimulation of beta-adrenergic receptors, in general,increases heart rate, the contractility of the heart and the rate ofconduction of electrical impulses through the AV node and the conductionsystem.

Drugs, drug formulations and/or drug compositions that may be usedaccording to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) beta-adrenergic receptorblocking agents. Beta-adrenergic receptor blocking agents orβ-adrenergic blocking agents are also known as beta-blockers orβ-blockers and as class II antiarrhythmics.

The term “beta-blocker” appearing herein may refer to one or more agentsthat antagonize the effects of beta-stimulating catecholamines byblocking the catecholamines from binding to the beta-receptors. Examplesof beta-blockers include, but are not limited to, acebutolol,alprenolol, atenolol, betantolol, betaxolol, bevantolol, bisoprolol,carterolol, celiprolol, chlorthalidone, esmolol, labetalol, metoprolol,nadolol, penbutolol, pindolol, propranolol, oxprenolol, sotalol,teratolo, timolol and combinations, mixtures and/or salts thereof.

The effects of administered beta-blockers may be reversed byadministration of beta-receptor agonists, e.g., dobutamine orisoproterenol.

The parasympathetic or cholinergic system participates in control ofheart rate via the sinoatrial (SA) node, where it reduces heart rate.Other cholinergic effects include inhibition of the AV node and aninhibitory effect on contractile force. The cholinergic system actsthrough the vagal nerve to release acetylcholine, which, in turn,stimulates cholinergic receptors. Cholinergic receptors are also knownas muscarinic receptors. Stimulation of the cholinergic receptorsdecreases the formation of cAMP. Stimulation of cholinergic receptorsgenerally has an opposite effect on heart rate compared to stimulationof beta-adrenergic receptors. For example, beta-adrenergic stimulationincreases heart rate, whereas cholinergic stimulation decreases it. Whenvagal tone is high and adrenergic tone is low, there is a marked slowingof the heart (sinus bradycardia). Acetylcholine effectively reduces theamplitude, rate of increase and duration of the SA node actionpotential. During vagal nerve stimulation, the SA node does not arrest.Rather, pacemaker function may shift to cells that fire at a slowerrate. In addition, acetylcholine may help open certain potassiumchannels thereby creating an outward flow of potassium ions andhyperpolarization. Acetylcholine also slows conduction through the AVnode.

Drugs, drug formulations and/or drug compositions that may be usedaccording to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) cholinergic agent. The term“cholinergic agent” appearing herein may refer to one or morecholinergic receptor modulators or agonists. Examples of cholinergicagents include, but are not limited to, acetylcholine, carbachol(carbamyl choline chloride), bethanechol, methacholine, arecoline,norarecoline and combinations, mixtures and/or salts thereof.

Drugs, drug formulations and/or drug compositions that may be usedaccording to this invention may include any naturally occurring orchemically synthesized cholinesterase inhibitor. The term“cholinesterase inhibitor” appearing herein may refer to one or moreagents that prolong the action of acetylcholine by inhibiting itsdestruction or hydrolysis by cholinesterase. Cholinesterase inhibitorsare also known as acetylcholinesterase inhibitors. Examples ofcholinesterase inhibitors include, but are not limited to, edrophonium,neostigmine, neostigmine methylsulfate, pyridostigmine, tacrine andcombinations, mixtures and/or salts thereof.

There are ion-selective channels within certain cell membranes. Theseion selective channels include calcium channels, sodium channels and/orpotassium channels. Therefore, other drugs, drug formulations and/ordrug compositions that may be used according to this invention mayinclude any naturally occurring or chemically synthesized calciumchannel blocker. Calcium channel blockers inhibit the inward flux ofcalcium ions across cell membranes of arterial smooth muscle cells andmyocardial cells. Therefore, the term “calcium channel blocker”appearing herein may refer to one or more agents that inhibit or blockthe flow of calcium ions across a cell membrane. The calcium channel isgenerally concerned with the triggering of the contractile cycle.Calcium channel blockers are also known as calcium ion influxinhibitors, slow channel blockers, calcium ion antagonists, calciumchannel antagonist drugs and as class IV antiarrhythmics. A commonlyused calcium channel blocker is verapamil.

Administration of a calcium channel blocker, e.g., verapamil, generallyprolongs the effective refractory period within the AV node and slows AVconduction in a rate-related manner, since the electrical activitythrough the AV node depends significantly upon the influx of calciumions through the slow channel. A calcium channel blocker has the abilityto slow a patient's heart rate, as well as produce AV block. Examples ofcalcium channel blockers include, but are not limited to, amiloride,amlodipine, bepridil, diltiazem, felodipine, isradipine, mibefradil,nicardipine, nifedipine (dihydropyridines), nickel, nimodinpine,nisoldipine, nitric oxide (NO), norverapamil and verapamil andcombinations, mixtures and/or salts thereof. Verapamil and diltiazem arevery effective at inhibiting the AV node, whereas drugs of thenifedipine family have a lesser inhibitory effect on the AV node. Nitricoxide (NO) indirectly promotes calcium channel closure. NO may be usedto inhibit contraction. NO may also be used to inhibit sympatheticoutflow, lessen the release of norepinephrine, cause vasodilation,decrease heart rate and decrease contractility. In the SA node,cholinergic stimulation leads to formation of NO.

Other drugs, drug formulations and/or drug compositions that may be usedaccording to this invention may include any naturally occurring orchemically synthesized sodium channel blocker. Sodium channel blockersare also known as sodium channel inhibitors, sodium channel blockingagents, rapid channel blockers or rapid channel inhibitors.Antiarrhythmic agents that inhibit or block the sodium channel are knownas class I antiarrhythmics, examples include, but are not limited to,quinidine and quinidine-like agents, lidocaine and lidocaine-likeagents, tetrodotoxin, encainide, flecainide and combinations, mixturesand/or salts thereof. Therefore, the term “sodium channel blocker”appearing herein may refer to one or more agents that inhibit or blockthe flow of sodium ions across a cell membrane or remove the potentialdifference across a cell membrane. For example, the sodium channel mayalso be totally inhibited by increasing the extracellular potassiumlevels to depolarizing hyperkalemic values, which remove the potentialdifference across the cell membrane. The result is inhibition of cardiaccontraction with cardiac arrest (cardioplegia). The opening of thesodium channel (influx of sodium) is for swift conduction of theelectrical impulse throughout the heart.

Other drugs, drug formulations and/or drug compositions that may be usedaccording to this invention may include any naturally occurring orchemically synthesized potassium channel agent. The term “potassiumchannel agent” appearing herein may refer to one or more agents thatimpact the flow of potassium ions across the cell membrane. There aretwo major types of potassium channels. The first type of channel isvoltage-gated and the second type is ligand-gated.Acetylcholine-activated potassium channels, which are ligand-gatedchannels, open in response to vagal stimulation and the release ofacetylcholine. Opening of the potassium channel causeshyperpolarization, which decreases the rate at which the activationthreshold is reached. Adenosine is one example of a potassium channelopener. Adenosine slows conduction through the AV node. Adenosine, abreakdown product of adenosine triphosphate, inhibits the AV node andatria. In atrial tissue, adenosine causes the shortening of the actionpotential duration and causes hyperpolarization. In the AV node,adenosine has similar effects and also decreases the action potentialamplitude and the rate of increase of the action potential. Adenosine isalso a direct vasodilator by its actions on the adenosine receptor onvascular smooth muscle cells. In addition, adenosine acts as a negativeneuromodulator, thereby inhibiting release of norepinephrine. Class IIIantiarrhythmic agents also known as potassium channel inhibitorslengthen the action potential duration and refractoriness by blockingthe outward potassium channel to prolong the action potential.Amiodarone and d-sotalol are both examples of class III antiarrhythmicagents.

Potassium is the most common component in cardioplegic solutions. Highextracellular potassium levels reduce the membrane resting potential.Opening of the sodium channel, which normally allows rapid sodium influxduring the upstroke of the action potential, is therefore inactivatedbecause of a reduction in the membrane resting potential.

Drugs, drug formulations and/or drug compositions that may be usedaccording to this invention may comprise one or more of any naturallyoccurring or chemically synthesized beta-blocker, cholinergic agent,cholinesterase inhibitor, calcium channel blocker, sodium channelblocker, potassium channel agent, adenosine, adenosine receptor agonist,adenosine deaminase inhibitor, dipyridamole, monoamine oxidaseinhibitor, digoxin, digitalis, lignocaine, bradykinin agents,serotoninergic agonist, antiarrythmic agents, cardiac glycosides, localanesthetics and combinations or mixtures thereof. Digitalis and digoxinboth inhibit the sodium pump. Digitalis is a natural inotrope derivedfrom plant material, while digoxin is a synthesized inotrope.Dipyridamole inhibits adenosine deaminase, which breaks down adenosine.Drugs, drug formulations and/or drug compositions capable of reversiblysuppressing autonomous electrical conduction at the SA and/or AV node,while still allowing the heart to be electrically paced to maintaincardiac output may be used according to this invention.

Beta-adrenergic stimulation or administration of calcium solutions maybe used to reverse the effects of a calcium channel blocker such asverapamil. Agents that promote heart rate and/or contraction may be usedin the present invention. For example, dopamine, a naturalcatecholamine, is known to increase contractility. Positive inotropesare agents that specifically increase the force of contraction of theheart. Glucagon, a naturally occurring hormone, is known to increaseheart rate and contractility. Glucagon may be used to reverse theeffects of a beta-blocker since its effects bypass the beta receptor.Forskolin is known to increase heart rate and contractility. Asmentioned earlier, epinephrine and norepinephrine naturally increaseheart rate and contractility. Thyroid hormone, phosphodiesteraseinhibitors and prostacyclin, a prostaglandin, are also known to increaseheart rate and contractility. In addition, methylxanthines are known toprevent adenosine from interacting with its cell receptors.

The drug delivery device may include a vasodilative delivery componentand/or a vasoconstrictive delivery component. Both delivery componentsmay be any suitable means for delivering vasodilative and/orvasoconstrictive drugs to a site of a medical procedure. For example,the drug delivery device may be a system for delivering a vasodilativespray and/or a vasoconstrictive spray. The drug delivery device may be asystem for delivering a vasodilative cream and/or a vasoconstrictivecream. The drug delivery device may be a system for delivering anyvasodilative formulation such as an ointment or medicament etc. and/orany vasoconstrictive formulation such as an ointment or medicament etc.or any combination thereof.

The drug delivery device may comprise a catheter, such as a drugdelivery catheter or a guide catheter, for delivering a vasodilativesubstance followed by a vasoconstrictive substance. A drug deliverycatheter may include an expandable member, e.g., a low-pressure balloon,and a shaft having a distal portion, wherein the expandable member isdisposed along the distal portion. A catheter for drug delivery maycomprise one or more lumens and may be delivered endovascularly viainsertion into a blood vessel, e.g., an artery such as a femoral,radial, subclavian or coronary artery. The catheter can be guided into adesired position using various guidance techniques, e.g., flouroscopicguidance and/or a guiding catheter or guide wire techniques. In oneembodiment, one catheter may be used to deliver both a vasodilativecomponent and a vasoconstrictive component. The drug delivery device maybe a patch, such as a transepicardial patch that slowly releases drugsdirectly into the myocardium, a cannula, a pump and/or a hypodermicneedle and syringe assembly. The drug delivery device may be aniontophoretic drug delivery device placed on the heart.

A vasodilative component may comprise one or more vasodilative drugs inany suitable formulation or combination. Examples of vasodilative drugsinclude, but are not limited to, a vasodilator, an organic nitrate,isosorbide mononitrate, a mononitrate, isosorbide dinitrate, adinitrate, nitroglycerin, a trinitrate, minoxidil, sodium nitroprusside,hydralazine hydrochloride, nitric oxide, nicardipine hydrochloride,fenoldopam mesylate, diazoxide, enalaprilat, epoprostenol sodium, aprostaglandin, milrinone lactate, a bipyridine and a dopamine D1-likereceptor agonist, stimulant or activator. The vasodilative component mayinclude a pharmaceutically acceptable carrier or solution in anappropriate dosage.

A vasoconstrictive component may comprise one or more suitablevasoconstrictive drugs in any suitable formulation or combination.Examples of vasoconstrictive drugs include, but are not limited to, avasoconstrictor, a sympathomimetic, methoxamine hydrochloride,epinephrine, midodrine hydrochloride, desglymidodrine, and analpha-receptor agonist, stimulant or activator. The vasoconstrictivecomponent may include a pharmaceutically acceptable carrier or solutionin an appropriate dosage.

Controller 16 may process sensed information from a sensor. Thecontroller may store and/or process such information before, duringand/or after a medical procedure, e.g., an ablation procedure. Forexample, the patient's tissue temperature may be sensed, stored andprocessed prior to and during the ablation procedure.

Controller 16 may be used to control the energy supplied to one or moreenergy transfer elements, e.g., electrodes or transducers, oftissue-engaging device 200 and/or ablation device 12. Controller 16 mayalso gather and process information from one or more sensors. Thisinformation may be used to adjust energy levels and times. Controller 16may incorporate one or more switches to facilitate regulation of thevarious system components by the surgeon. One example of such a switchis a foot pedal. A switch may also be, for example, a hand switch, or avoice-activated switch comprising voice-recognition technologies. Aswitch may be physically wired to controller 16 or it may be a remotecontrol switch. A switch may be incorporated in or on one of thesurgeon's instruments, such as surgical site retractor, e.g., a sternalor rib retractor, tissue-engaging device 200 and/or ablation device 12,or any other location easily and quickly accessed by the surgeon.Controller 16 may also include a display. Controller 16 may also includeother means of indicating the status of various components to thesurgeon such as a numerical display, gauges, a monitor display or audiofeedback.

Controller 16 may incorporate a cardiac stimulator and/or cardiacmonitor. For example, electrodes used to stimulate or monitor the heartmay be incorporated into tissue-engaging device 200 and/or ablationdevice 12. Controller 16 may incorporate a nerve stimulator and/or nervemonitor. For example, electrodes used to stimulate or monitor one ormore nerves, e.g., a vagal nerve, may be incorporated intotissue-engaging device 200 and/or ablation device 12. Controller 16 maycomprise a surgeon-controlled switch for cardiac stimulation and/ormonitoring, as discussed earlier. Controller 16 may comprise asurgeon-controlled switch for nerve stimulation and/or monitoring, asdiscussed earlier. Cardiac stimulation may comprise cardiac pacingand/or cardiac defibrillation. Controller 16, tissue-engaging device 200and/or ablation device 12 may incorporate a cardiac mapping device formapping the electrical signals of the heart.

A visual and/or audible signal used to alert a surgeon to the completionor resumption of energy delivery, suction, sensing, monitoring,stimulation and/or delivery of fluids, drugs and/or cells may beincorporated into controller 16. For example, a beeping tone or flashinglight that increases in frequency as the energy delivered increases.

System 900 may include sensor 600. Sensor 600 may be incorporated intotissue-engaging device 200 and/or ablation device 12 or it may beincorporated into another separate device. A separate sensor device maybe positioned and used, for example, through a thoracotomy, through asternotomy, percutaneously, transvenously, arthroscopically,endoscopically, for example, through a percutaneous port, through a stabwound or puncture, through a small incision, for example, in the chest,in the groin, in the abdomen, in the neck or in the knee, or incombinations thereof.

Sensor 600 may comprise one or more switches, e.g., a surgeon-controlledswitch. One or more switches may be incorporated in or on a sensordevice or any other location easily and quickly accessed by the surgeonfor regulation of sensor 600 by the surgeon. A switch may be, forexample, a hand switch, a foot switch, or a voice-activated switchcomprising voice-recognition technologies. A switch may be physicallywired to sensor 600 or it may be a remote control switch.

Sensor 600 may include a visual and/or audible signal used to alert asurgeon to any change in the measured parameter, for example, tissuetemperature, cardiac hemodynamics or ischemia. A beeping tone orflashing light may be used to alert the surgeon that a change hasoccurred in the parameter sensed.

Sensor 600 may comprise one or more temperature-sensitive elements, suchas a thermocouple, to allow a surgeon to monitor temperature changes ofa patient's tissue. Alternatively, sensor 600 may sense and/or monitorvoltage, amperage, wattage and/or impedance. For example, an ECG sensormay allow a surgeon to monitor the hemodynamics of a patient during aheart positioning procedure. The heart may become hemodynamicallycompromised during positioning and while in a non-physiologicalposition. Alternatively, sensor 600 may be any suitable blood gas sensorfor measuring the concentration or saturation of a gas in the blood ortissues. For example, sensor 600 may be a sensor for measuring theconcentration or saturation of oxygen or carbon dioxide in the blood ortissues. Alternatively, sensor 600 may be any suitable sensor formeasuring blood pressure or flow, for example a Doppler ultrasoundsensor system, or a sensor for measuring hematocrit (HCT) levels.

Alternatively sensor 600 may be a biosensor, for example, comprising animmobilized biocatalyst, enzyme, immunoglobulin, bacterial, mammalian orplant tissue, cell and/or subcellular fraction of a cell. For example,the tip of a biosensor may comprise a mitochondrial fraction of a cell,thereby providing the sensor with a specific biocatalytic activity.

Sensor 600 may be based on potentiometric technology or fiber optictechnology. For example, the sensor may comprise a potentiometric orfiber optic transducer. An optical sensor may be based on either anabsorbance or fluorescence measurement and may include an UV, a visibleor an IR light source.

Sensor 600 may be used to detect naturally detectable propertiesrepresentative of one or more characteristics, e.g., chemical, physical,mechanical, thermal, electrical or physiological, of system 900 and/or apatient's bodily tissues or fluids. For example, naturally detectableproperties of patient's bodily tissues or fluids may include pH, fluidflow, electrical current, impedance, temperature, pressure, tension,components of metabolic processes, chemical concentrations, for example,the absence or presence of specific peptides, proteins, enzymes, gases,ions, etc. Naturally detectable properties of system 900 may include,for example, pressure, tension, stretch, fluid flow, electrical,mechanical, chemical and/or thermal. For example, sensor 600 may be usedto sense, monitor and/or control suction or vacuum delivered fromsuction source 300. Sensor 600 may be used to measure suction betweendevice 200 and tissue. Sensor 600 may be used to sense, monitor and/orcontrol fluid delivered from fluid source 400. Sensor 600 may be used tosense, monitor and/or control energy delivered from power supply 14 viacontroller 16.

Sensor 600 may include one or more imaging systems, camera systemsoperating in UV, visible, or IR range; electrical sensors; voltagesensors; current sensors; piezoelectric sensors; electromagneticinterference (EMI) sensors; photographic plates, polymer-metal sensors;charge-coupled devices (CCDs); photo diode arrays; chemical sensors,electrochemical sensors; pressure sensors, vibration sensors, sound wavesensors; magnetic sensors; UV light sensors; visible light sensors; IRlight sensors; radiation sensors; flow sensors; temperature sensors; orany other appropriate or suitable sensor.

Sensor 600 may be incorporated into tissue-engaging device 200 and/orablation device 12 or sensor 600 may be placed or used at a locationdiffering from the location of tissue-engaging device 200 and/orablation device 12. For example, sensor 600 may be placed in contactwith the inside surface of a patient's heart while tissue-engagingdevice 200 and/or ablation device 12 is placed or used on the outsidesurface of the patient's heart.

Ablation assembly 10, tissue-engaging device 200, suction source 300,fluid source 400, drug delivery device and/or processor 800 may beslaved to sensor 600. For example, tissue-engaging device 200 may bedesigned to automatically adjust suction if sensor 600 measures apredetermined sensor value, e.g., a particular suction value, orablation device 12 may be designed to stop or start the ablation oftissue if sensor 600 measures a predetermined sensor value, e.g., aparticular tissue temperature.

Sensor 600 may include a visual and/or audible signal used to alert asurgeon to any change in the one or more characteristics the sensor issensing and/or monitoring. For example, a beeping tone or flashing lightthat increases in frequency as tissue temperature rises may be used toalert the surgeon.

Controller 16 may include one or more processors. A processor mayreceive and preferably interpret the signal from sensor 600. A processormay comprise software and/or hardware. A processor may comprise fuzzylogic. A suitable amplifier may amplify signals from sensor 600 beforereaching a processor. The amplifier may be incorporated into aprocessor. Alternatively the amplifier may be incorporated into sensor600 or tissue-engaging device 200 or ablation device 12. Alternatively,the amplifier may be a separate device. A processor may be a deviceseparate from ablation assembly 10, tissue-engaging device 200, suctionsource 300, fluid source 400, sensor 600 and/or imaging device 800. Aprocessor may be incorporated into ablation device 12, tissue-engagingdevice 200, suction source 300, fluid source 400, sensor 600 and/orimaging device 800. A processor may control the energy delivered fromthe power supply 14. For example, a signal of a first intensity fromsensor 600 may indicate that the energy level from power supply 14should be lowered; a signal of a different intensity may indicate thatpower supply 14 should be turned off. Preferably, a processor may beconfigured so that it may automatically raise or lower the suctiondelivered to device 12 and/or device 200 from suction source 300, thefluids delivered to device 12 and/or device 200 from fluid source 400and/or the energy delivered to device 12 and/or device 200 from powersupply 14. Alternatively, the control of suction source 300, fluidsource 400 and/or power supply 14 based on output from a processor maybe manual.

Controller 16 may include a visual display or monitor, such as, forexample, a LCD or CRT monitor, to display various amounts and types ofinformation. By software control, the user may choose to display theinformation in a number of ways. The monitor may show, for example, acurrently sensed parameter, e.g., temperature. The monitor may also lockand display the maximum sensed value achieved. Sensed information may bedisplayed to the user in any suitable manner, such as for example,displaying a virtual representation of ablation device 12 and/ortissue-engaging device 200 on the monitor.

Alternatively, the monitor may display the voltage corresponding to thesignal emitted from sensor 600. This signal corresponds in turn to theintensity of a sensed parameter at the target tissue site. Therefore avoltage level of 2 would indicate that the tissue was, for example,hotter than when the voltage level was 1. In this example, a user wouldmonitor the voltage level and, if it exceeded a certain value, wouldturn off or adjust the power supply 14.

The display of controller 16 may alternatively be located on ablationdevice 12, power supply 14, tissue-engaging device 200, suction source300, fluid source 400, sensor 600 and/or imaging device 800. Anindicator, such as an LED light, may be permanently or removeablyincorporated into ablation device 12, power supply 14, tissue-engagingdevice 200, suction source 300, fluid source 400, sensor 600 and/orimaging device 800. The indicator may receive a signal from sensor 600indicating that the tissue had reached an appropriate value, for exampletemperature. In response, the indicator may turn on, change color, growbrighter or change in any suitable manner to indicate that the flow ofenergy from power supply 14 should be modified or halted. The indicatormay also be located on ablation device 12, power supply 14,tissue-engaging device 200, suction source 300, fluid source 400, sensor60 and/or imaging device 800 and/or may be located on another locationvisible to the user.

Controller 16 may include an audio device that indicates to the userthat the delivery of suction, fluids and/or energy should be halted oradjusted. Such an audio device may be, for example, a speaker thatbroadcasts a sound (for example, a beep) that increases in intensity,frequency or tone as a parameter sensed by sensor 600 increases. Theuser may adjust, for example, turn down or turn off power supply 14 whenthe sound emitted reaches a given volume or level. In anotherembodiment, the audio device may also give an audible signal (such asthe message “turn off energy source”), for example, when a parametersensed by sensor 600 reaches a certain level. Such an audio device maybe located on tissue-engaging device 200, suction source 300, fluidsource 400, sensor 600 and/or imaging device 800. The audio device mayalso be a separate device.

In one embodiment of the present invention, system 900 may include animaging device 800. Imaging device 800 may be based on one or moreimaging modalities such as ultrasound imaging, CT, MRI, PET,fluoroscopy, echocardiography, etc. The coordinates for the desired areaof ablation, for example, from any of these imaging modalities can beelectronically fed to controller 16 such that the desired ablationpattern can be generated and ablated. The imaging device may have twoand/or three-dimensional imaging capabilities as well as phased and/orannular array imaging capabilities. For example, two orthree-dimensional echocardiography, such as transesophagealechocardiography (TEE), or ultrasound imaging, such as transthoracicultrasound imaging may be possible with use of imaging device 800.

The imaging device may comprise one or more light sources and/orilluminating materials, e.g., glow-in-the-dark materials. For example,the tissue-engaging head of device 200 and/or one or more portions ofablation device 12 may comprise one or more glow-in-the-dark materials.The imaging device may be based on fluorescence technologies. Theimaging device may comprise fiber optic technologies; for example afiber optic conduit may deliver light from a remote light source to anarea adjacent tissue-engaging device 200 and/or ablation device 12 forillumination of a treatment site.

The imaging device may comprise a light pipe, for example, to illuminatethe tissue-engaging head of device 200 and/or ablation device 12 and/orthe surgical field adjacent device 200 and/or device 12. A transparent,semi-transparent or translucent tissue-engaging head may be illuminatedmerely by placement of the end of a light pipe or other light sourceadjacent the tissue-engaging head of device 200. A transparent,semi-transparent or translucent portion of ablation device 12 may beilluminated merely by placement of the end of a light pipe or otherlight source adjacent the transparent, semi-transparent or translucentportion of ablation device 12.

The imaging device may include a visual display or monitor, such as, forexample, a LCD or CRT monitor, to display various amounts and types ofinformation. By software control, the user may choose to display theinformation in a number of ways. The imaging device may be powered by ACcurrent, DC current, or it may be battery powered either by a disposableor re-chargeable battery. The imaging device may provide UV, IR and/orvisible light. The imaging device may include a laser. The imagingdevice may be incorporated into tissue-engaging device 200 and/orablation device 12 or it may be incorporated into a separate device. Aseparate imaging device may be positioned and used, for example, througha thoracotomy, through a sternotomy, percutaneously, transvenously,arthroscopically, endoscopically, for example, through a percutaneousport, through a stab wound or puncture, through a small incision, forexample, in the chest, in the groin, in the abdomen, in the neck or inthe knee, or in combinations thereof. A separate imaging device may bepositioned through one or more body cavity openings of the patientand/or positioned outside the patient, e.g., on the skin of the patient.One or more imaging devices may be positioned in the esophagus, thetrachea and/or the bronchi of the lungs.

The imaging device may comprise one or more switches, e.g., asurgeon-controlled switch. One or more switches may be incorporated inor on the imaging device or any other location easily and quicklyaccessed by the surgeon for regulation of the imaging device by thesurgeon. A switch may be, for example, a hand switch, a foot switch, ora voice-activated switch comprising voice-recognition technologies. Aswitch may be physically wired to the imaging device or it may be aremote control switch.

Ablation assembly 10, tissue-engaging device 200, suction source 300,fluid source 400, a drug delivery device and/or imaging device may beslaved to a robotic system or a robotic system may be slaved to ablationassembly 10, tissue-engaging device 200, suction source 300, fluidsource 400, sensor 60, a drug delivery device and/or imaging device.Computer- and voice-controlled robotic systems that position andmaneuver endoscopes and/or other surgical instruments for performingmicrosurgical procedures through small incisions may be used by thesurgeon to perform precise and delicate maneuvers. These robotic systemsmay allow the surgeon to perform a variety of microsurgical procedures.In general, robotic systems may include head-mounted displays whichintegrate 3-D visualization of surgical anatomy and related diagnosticand monitoring data, miniature high resolution 2-D and 3-D digitalcameras, a computer, a high power light source and a standard videomonitor.

A medical procedure wherein one or more components of system 900 may beused may be non-invasive, minimally invasive and/or invasive. Themedical procedure may entail a port-access approach, a partially ortotally endoscopic approach, a sternotomy approach or a thoracotomyapproach. The medical procedure may include the use of various roboticor imaging systems. The medical procedure may be surgery on the heart.Alternatively, the medical procedure may be surgery performed on anotherorgan of the body.

In one embodiment of the present invention, a positioning ortissue-engaging device may comprise one or more sensors and/orelectrodes, e.g., sensing electrodes and/or stimulation electrodes. Inanother embodiment of the present invention, an imaging device maycomprise one or more sensors and/or electrodes, e.g., sensing electrodesand/or stimulation electrodes. In another embodiment of the presentinvention, a positioning or tissue-engaging device may comprise imagingcapabilities, e.g., ultrasound imaging, and one or more sensors and/orelectrodes, e.g., sensing electrodes and/or stimulation electrodes.

In one embodiment of the present invention, an ablation device maycomprise one or more sensors and/or electrodes, e.g., sensing electrodesand/or stimulation electrodes. In another embodiment of the presentinvention, an ablation device may comprise imaging capabilities, e.g.,ultrasound imaging, and/or one or more electrodes, e.g., stimulationelectrodes. In another embodiment of the present invention, an ablationdevice may comprise tissue-positioning capabilities, e.g., suctionengagement of tissue. In one embodiment of the invention, ablationdevice 12 may be guided or steerable.

In one embodiment of the present invention, transducer elements 28 maycomprise one or more configurations varying in size and shape. Forexample, transducer elements 28 may be round, as shown in FIG. 2.Alternatively, transducer elements 28 may be elongated or linear inshape, as shown in FIGS. 18 and 19. Transducers elements 28 may bearranged on or in housing 26 in various configurations. In FIG. 2, forexample, transducers elements 28 are shown arranged in a planar array ofthree rows R and six columns C, although the transducer elements can bearranged in any number of rows and columns. Alternatively, thetransducer elements may be angled to a more central area to create alesion of a desired shape rather than in a row aimed along the sameaxis. In FIG. 19, elongated transducer elements 28 are shown arrangedalong a curve. Housing 26 may be configured to have one or more shapes,such as a round shape, an oval shape, a square shape, a rectangularshape, a triangular shape, a concave cave shape, a convex shape, a flatshape, etc. In FIG. 2, for example, housing 26 is shown to have a flat,rectangular shape. Alternatively, in FIGS. 18 and 19, for example,housing 26 is shown to have a concave, rectangular shape. The transducerelements 28, in FIG. 19, are shown aligned relatively parallel to eachother. Linear transducer elements as shown in FIGS. 18 and 19 would becapable of producing a line of focused energy.

In one embodiment of the present invention, devices, systems, andmethods that may be used for guidance of a medical device, e.g., anablation device, in a minimally invasive medical procedure, includeelectromagnetic devices, systems and methods, electric field devices,systems and methods, and ultrasound devices, systems and methods.Examples of various tracking, monitoring, positioning, guiding and/ornavigating technologies are disclosed in U.S. Pat. Nos. 5,782,765;6,190,395; 6,235,038; 6,379,302; 6,381,485; 6,402,762; 6,434,507;6,474,341; 6,493,573; 6,636,757; 6,669,635; 6,701,179; 6,725,080, theentire disclosures of which are incorporated herein by reference.

A guidance device, system, and/or method that may be used according toone embodiment of the invention include the use of electrical fields,for example, electric fields passing in three axes through a patient'sbody. In one embodiment, three pairs of sensors, e.g., electrodepatches, are positioned in electrical contact with the patient's body.In one embodiment, one set of the electrode patch sensors are orientedin each of the three axes, side-to-side, front-to-back, and head-to-toe,e.g., electrode patch sensors located on neck and thigh. A 40.1 KHz,40.2 KHz, and 40.3 KHz signal is transmitted, for example, between eachof the three sets of electrode patch sensors, respectively. The threesignals transmitted between the electrode patch sensors, may be pickedup by sensors, e.g., electrodes, positioned on medical devices placedwithin the patient's body, e.g., within the patient's cardiovascularsystem or thoracic cavity. Sensor electrodes that are in contact withelectrically conductive tissue and/or fluids, e.g., blood, may bemonitored from outside of the body via the three signals transmittedbetween the three pairs of electrode patch sensors, since there will bea voltage drop across each of the three inter-patch spaces within thebody associated with electrodes of the medical devices. The voltage dropmay be used to calculate the location of the monitored sensorelectrode(s) in 3-D space within the patient's body. One embodiment ofan electric field guidance device may track the position of up to 10sensor electrodes simultaneously. An electric field guidance device orsystem may include a visual monitor or display to display electrodelocations or positions. For example, the monitored sensor electrodes maybe shown on a three axis coordinate grid on a monitor or display. In oneembodiment, the electric field guidance device achieves the bestaccuracy when the electric field gradients are uniform. Distortions tothe electric fields may cause inaccuracies in the rendered position ofthe electrodes. Electric field distortions may be caused by air voids,for example, within the thoracic cavity. Therefore, sensor electrodesthat are being tracked should maintain contact with conductive tissueand/or fluids to have their positions monitored continuously, forexample, on the coordinate system.

A guidance device, system, and/or method may use one or more imagingdevices to acquire images, for example, previously acquired ultrasound,CT, MRI, PET, fluoroscopy and/or echocardiography images, to providereal-time medical device monitoring, positioning, tracking and/orguidance. Previously acquired images may be registered to the patient.For example, acquired images of anatomical structures of the patient maybe accurately registered to the patient's anatomy in real-time. Theguidance device or system may then show, for example, on a visualmonitor or display, the locations or positions of the medical devicesensors relative to a previously acquired image or images, therebyproviding real-time monitoring, positioning, tracking and/or guidance ofthe medical device or devices relative to an image or images of thepatient's anatomy.

A guidance device, system, and method that may be used according to oneembodiment of the invention include the use of a magnetic field. In oneembodiment, sensors comprising three small coils are positioned andoriented in three different axes of a medical device, e.g., an ablationdevice, and a sensor, e.g., an antenna pad, is placed in contact withthe patient's body, for example, the antenna sensor pad is placed underthe patient. The magnetic field guidance device and method senses the3-D location of the three sensor coils of the medical device. The 3-Dlocation of the sensor coils may then be displayed or represented on avisual monitor or display, for example, as shown on a three axiscoordinate grid. Again, the guidance device, system, and/or method mayuse one or more imaging devices to acquire images to provide real-timemedical device monitoring, positioning, tracking and/or guidance. Forexample, a device comprising sensor coils may be monitored as theportion of the device comprising the sensor coils is moved around aspace, cavity or chamber, e.g., a cardiac chamber, within the patient.The geometry of the space, cavity or chamber may then be mapped anddisplayed, for example, on a visual monitor or display. The accuracy ofthe geometric mapping of a space, cavity or chamber is generally relatedto the number of data points collected or monitored. A magnetic fieldguidance device or system is generally not sensitive to air voids withinthe patient's body.

A guidance device and method that may be used according to oneembodiment of the invention includes the use of ultrasound. In oneembodiment, sensors comprising ultrasound transducers are incorporatedinto a medical device, e.g., an ablation device. The ultrasoundtransducer sensors of the medical device to be tracked emit ultrasonicenergy. The ultrasonic energy is then received by ultrasonic transducersensors on other devices within the patient's body or in contact withthe patient's body. The ultrasound guidance device may then display therelative positions of one or more of the ultrasound transducer sensorsand renders images of the devices incorporating the ultrasoundtransducer sensors. Again, the guidance device, system, and/or methodmay use one or more imaging devices to acquire images to providereal-time medical device monitoring, positioning, tracking and/orguidance. The 3-D location of the ultrasound transducer sensors may bedisplayed or represented on a visual monitor or display, for example, asshown on a three axis coordinate grid layered onto a previously acquiredimage. The ultrasound guidance device or system can be very sensitive toair voids or differences in the speed of sound within various types oftissues and/or fluids.

A guidance device, system, and method that may be used according to oneembodiment of the invention include the use of an electromagnetic fieldtransmitter that may be coupled to an image intensifier of afluoroscopic imaging device, e.g., a fluoroscope. In one embodiment, theguidance device or system may transmit three alternating magnetic fieldsthat may be received by coils within the field of interest. Theelectromagnetic field transmitter may contain a matrix of small metalspheres that may be used to normalize a fluoroscopic image. In oneembodiment, fluoroscopic images are acquired in one or more directionalorientations using a fluoroscopic imaging device or system. The acquiredimages are then viewed by a physician who is then able to track andguide a medical device within the field of interest. In one embodiment,each medical device tracked and/or guided comprises at least onereceiving sensor coil that allows the medical device to which it isattached to be tracked in 3D space with respect to the previouslyacquired fluoroscopic image or images.

In embodiment of the present invention, previously acquired images,e.g., images of a patient's thoracic cavity, acquired by one or moreimaging devices may be displayed while displaying images and preciselocations of one or more medical devices inserted into the patient,e.g., the patient's thoracic cavity. The medical devices may be handheld, manually controlled, remotely controlled, e.g., by magneticfields, and/or robotically controlled. Each medical device that is to betracked in real-time comprises at least one sensor coil. In oneembodiment, electromagnetic navigation or guidance technology utilizes asystem that transmits three separate electromagnetic fields that aresensed by a single sensor coil or multiple sensor coils mounted on themedical device to be tracked. In one embodiment, each medical device tobe monitored and/or tracked in 3-D space requires at least one sensorcoil. Additional medical device sensor coils may provide detailsregarding the shape and/or path of the medical device, for example. Theshape of a flexible and/or articulating portion of a medical device maybe provided via sensor coils positioned on or within the flexible and/orarticulating portion. For example, an elongated flexible member of amedical device may have multiple sensor coils positioned along itslength. In one embodiment, accurate registration of a previouslyacquired anatomical image may be performed using surface fiducialregistration points as well as internal, implanted and/or indwellingreference devices. The form of reference points required to register theimage to the true anatomy may depend on the accuracy needed for theparticular procedure and anatomy of interest. In terms of informationmanagement to the surgeon, one embodiment of this invention couplesvisual imaging, e.g., endoscopic imaging, with navigation or guidancethrough the virtual anatomy.

One embodiment of the present invention involves first imaging of thepatient's area of interest, e.g., the patient's thoracic cavity anatomy,using, for example, one or more plane fluoroscopy, computed tomography(CT), magnetic resonance (MR) imaging, and/or one or more plane 2-D or3-D ultrasound imaging prior to the procedure. The initial imaging maybe carried out by first placing fiduciary markers on specific points onor in the patient's body. The fiduciary markers may be easily identifiedon the images via use of one or more contrast agents or materialsidentifiable to the particular imaging technique used. The fiduciarymarkers may be attached to the skin, positioned subcutaneously,implanted, positioned in the trachea, bronchi, and/or esophagus, or maybe inserted into the cardiovascular system, for example. In oneembodiment, a medical device, e.g., a catheter or catheter-like device,having multiple sensor coils may be placed through the venous systemthrough the inferior vena cava and/or superior vena cava and extendedinto various additional portions of the right side of the heart, e.g.,the right atrial appendage, the coronary sinus, the right ventricle, theinter-ventricular septum, the right ventricular apex, the rightventricular outflow tract, and/or the pulmonary arteries. In oneembodiment, delivery to sites such as the pulmonary arteries may beaided by the addition of a balloon positioned at or near the distal endof the fiduciary marking device to make use of blood flow to force thedevice downstream into the distal end of the right side of thecardiovascular system and into one or more of the pulmonary arteries.Additionally, such a fiduciary marking device may be placed in thearterial side of the cardiovascular system, whereby it may be introducedvia an artery into the ascending aorta and extended through thedescending aorta (or into superior arterial vessels) and into the aorticvalve, the left ventricle, the inter-ventricular septum, the leftventricular apex, the mitral valve annulus, the left atrium, the leftatrial appendage, and/or the pulmonary veins. In one embodiment, on ormore fiduciary devices inserted into the esophagus and/or trachea may beused to track in-real time respiration effects on the posterior aspectsof the heart. One or more reference sensor coils or marking points maybe incorporated into a tracheal tube used for a patient on a respirator.One or more reference sensor coils or marking points may be incorporatedinto an esophageal tube. An esophageal reference may provide informationof the location or position of the esophagus during procedures, e.g.,involving ablation of regions of the left atrium. The location orposition of the esophagus, for example, during an ablation procedure maybe valuable to prevent or minimize any damage that could occur duringthe delivery of an ablation therapy.

In one embodiment, the guidance device or system may include one or morefiducial marking and/or reference devices. The fiducial marking andreference devices may be placed, for example, in and around the heart,e.g., endocardially, epicardially and/or in the pericardial space, todefine the real-time precise location of the heart's surfaces andstructures. An imaging device may be used to perform an imagingtechnique while one or more fiduciary marking and reference devices arepositioned at one or more locations. Imaging may be performed withregard to respiration and/or cardiac cycle of the patient, such that themotions associated with respiration and/or the beating of the heart maybe accounted for during the timing of the acquisition of the images.Placement of fiduciary marking and reference devices may be determinedby the physician according to the anatomy of interest where the highestaccuracy of the medical devices with respect to the anatomicalstructures is required. Placements of fiduciary marking and referencedevices may be performed using fluoroscopy.

In one embodiment, the guidance device or system may be used during aheart valve replacement or repair procedure. For example, a pulmonicvalve replacement procedure using a transvascular approach may involvepreliminary imaging with an imaging device, wherein imaging is performedwith skin surface fiduciary markers and a fiduciary marking catheterdevice placed through the venous system into the right ventricularoutflow tract and to the site of the pulmonic valve annulus. After thepreliminary imaging is complete and the patient is in the operatingroom, the pre-acquired image is then registered to the patient using thesurface fiduciary markers as well as the internal catheter to providehigh accuracy in the region of critical interest at the pulmonic valveannulus. The fiduciary catheter device may then be removed and a valvedelivery and deployment device may be advanced into the site of thepulmonic valve for delivery and deployment of a replacement valve.During valve delivery and deployment, a physician may use the imageguidance navigation device or system to view the real-time location andadvancement of the valve delivery and deployment device and to view itsmotion through the cardiovascular system all the way to the site ofdeployment at the pulmonic valve annulus, for example.

In one embodiment, the guidance device or system may be used during aminimally invasive ablation procedure, e.g., an epicardial ablationprocedure, to treat, for example, atrial fibrillation. One suchprocedure may involve the dissection and/or retraction of tissue to forma path around the cardiac anatomy through which an ablation device maybe placed to create one or more ablation lesions from the epicardialaspect. In one embodiment of the present invention, the ablationprocedure may be performed from the right side of the patient. One ormore structures that may be of interest to a surgeon upon entry into apatient's thoracic cavity, e.g., entry through a small incision or portaccess, may be the location of the pericardial sac and associatedstructures such as the phrenic nerve. Also of interest may be thelocation and courses of the caval veins, i.e., the inferior and superiorvena cava, the pulmonary arteries, and/or the pulmonary veins. In oneembodiment, the caval veins and other structures may be registered toone or more pre-acquired images using fiducial marking devices placed inthe venous cardiovascular system. In one embodiment, the pericardialreflections that are located between the superior pulmonary veins areseparated. In this region, a surgeon must be careful to avoid damage tothe atrial walls, pulmonary veins, and in particular, the pulmonaryarteries. Therefore, it may be advantageous to place a fiduciary markingdevice into one or more of the pulmonary arteries to ensure preciseregistration of these structures upon start of the procedure in theoperating room. Such precise location registration may greatly aid thesurgeon in performance of the dissections of these pericardialreflections. In one embodiment, the location of the lung surface may beof interest. In one embodiment, the tracking of the lung surface may beperformed via placement of one or more devices comprising one or moretracking sensor coils on the surface of the lung. In one embodiment, animaging device, e.g., an endoscopic camera and/or light guide, may beused to allow visual imaging of the surgical site or sites. The imagingdevice may be used to produce one or more images that may be displayedon a monitor. The one or more images may be coupled with the visualdisplay produced from a guidance or navigation device or system. Theimaging device may comprise one or more sensor coils, thereby allowingat least a portion of the imaging device to be tracked and/or guided in3-D space by the guidance or navigation device or system. The visualdisplay produced by the guidance device may be coupled in an appropriatemanner to the visual display produced by the imaging device, therebyproviding a physician with real-time monitoring of the imaging deviceand, thereby providing additional information to allow the physician toeasily identify anatomical structures located in the viewing area of theimaging device. In one embodiment, imaging devices may be equipped withone or more sensor coils of a guidance system, thereby allowing distaland proximal portions to be identified easily. For example, flexibleand/or deflectable medical devices may require multiple sensors, e.g.,sensor coils, to define the location and path of multiple portions ofthe medical device, e.g., the proximal and distal portions of a flexibleand/or deflectable distal medical device.

In one embodiment, sensors may be incorporated in one or more medicaldevices. A sensor may be attached or coupled directly to the surface ofa medical device. A sensor may be incorporated into a medical device. Asensor may be incorporated into a removable sheath, cover or insert thatmay be placed over or inserted into at least a portion of a medicaldevice. A removable sensor sheath, cover or insert may be disposable orre-useable. A sheath or cover may serve to protect one or more portionsof a medical device from one or more body fluids and/or tissues. Asheath or cover may comprise one or more lumens that allow suction,irrigation, and/or passage of guide-wires, catheters or similarflexible, and/or polymeric devices through the sheath and into theworking region at the distal end of the medical device. In oneembodiment, the guidance device or system may be used during a procedureof guiding, delivery and placement of a stent-graft, e.g., to repair ananeurism, e.g., an abdominal aortic aneurism and/or a thoracic aorticaneurism. In one embodiment, an imaging device or system may be used toacquire a detailed CT or MRI scan of the aortic arterial system, notonly to show the aneurism in detail, but to identify the branch sites ofnumerous arteries. The branch arteries of interest may include thecarotid, brachiocephalic trunk, subclavian, bronchial, phrenic, hepatic,cephalic trunk, splenic, mesenteric, renal, lumbar, and iliac arteries.It is generally important to identify these branch arteries and theirlocations prior to placement of a stent-graft so as to not to occludeany of them during the stent-graft placement procedure. In oneembodiment, the delivery stent-graft delivery device may be equippedwith one or more sensor coils to allow precise tracking and guidance ofthe delivery system through the aortic anatomy. A previously acquiredimage would be critical in determining the optimal stent-graft placementsite that may prevent further distension and rupture. During aprocedure, branch artery locations would be avoided whenever possiblebut when the stent-graft placement does cause an occlusion to occur, apreviously acquired image may be used to guide the placement of aperforation device and side branch perfusion channel to supply theoccluded artery through the wall of the stent-graft.

In one embodiment, one or more images of a patient's anatomy may beproduced using one or more imaging device, e.g., an x-ray device, afluoroscopy device, a CT device, a MRI device, a PET device and/or anultrasound imaging device. These images may be used in combination withtracked positions of one or more medical devices placed in a patient.These medical devices may be tracked using one or more guidance devicescomprising, for example, one or more sensors. The medical devices mayalso comprise one or more sensors. In one embodiment, a computergenerated display showing a medical device's position created by aguidance device or system may be superimposed on a previously acquiredimage or images produced by one or more imaging devices. In oneembodiment, a guidance device or system may include one or more imagingdevices. In one embodiment, a guidance device or system may include acontroller, e.g., a controller as discussed above. In one embodiment, aguidance device or system may include one or more sensors, e.g., whereinthe sensors are coupled to a controller. In one embodiment, a guidancedevice or system may be slaved to a robotic system or a robotic systemmay be slaved to a guidance device or system.

In one embodiment, a method of real-time image registration includesmonitoring in real-time fixed surface and indwelling fiduciary markingdevices so as to update and correct the registration of previouslyacquired images, e.g., x-ray images, fluoroscopy images, CT images, MRIimages, PET images and/or ultrasound images, thereby providing real-timechanges in position of the anatomical structures of interest, e.g.,respiration, cardiac motion, and intestinal peristalsis.

In one embodiment, a guidance device or system may comprise anelectrical sensor, a magnetic field sensor, an optical sensor, anacoustic sensor and/or an inertial sensor. In one embodiment, a guidancedevice or system may comprise a magnetic field generator. In oneembodiment, a sensor coil may comprise an electrically conductive,magnetically sensitive element that may be responsive to time-varyingmagnetic fields for generating induced voltage signals as a function of,and representative of, the applied time-varying magnetic field.

One embodiment of the present invention comprises an ablation devicehaving one or more ablating elements, e.g. electrodes, ultrasoundtransducers, microwave elements, cryo-ablation elements, and/or laserelements and one or more sensors, e.g., receiving sensor coils thatallow electromagnetic tracking and navigation in 3-D space of thelocation of one or more of the ablating elements of the ablation device.In one embodiment, the ablation device is a monopolar ablation device.In one embodiment, the ablation device is a bipolar ablation device. Inone embodiment, the ablation device is a surgical ablation device. Inone embodiment, the ablation device is a minimally invasive deviceand/or an endoscopic device. In one embodiment, the ablation devicecomprises one or more portions that are flexible, articulating,malleable and/or rigid.

One embodiment of the present invention includes one or more fiduciarymarking or reference devices that may be used to update and correct theregistration of previously acquired images, e.g., x-ray images,fluoroscopy images, CT images, MRI images, PET images and/or ultrasoundimages, thereby providing real-time changes in position of theanatomical structures of interest, e.g., respiration, cardiac motion,and intestinal peristalsis. In one embodiment, a fiduciary marking orreference device is visualizable and/or detectable by one or more meansof non-invasive imaging such as x-ray, fluoroscopy, computed tomography,magnetic resonance, PET and/or ultrasound imaging. In one embodiment,the fiduciary marking or reference device may include one or moresensors, e.g., sensor coils, thereby allowing the device's location in3-D space to be easily determined and used as a reference and/orreal-time registration point or points for tracking, navigation and/orguidance, e.g., electromagnetic tracking, navigation and/or guidance, in3-D space.

One embodiment of the present invention includes a fiduciary referenceor marking device which may be fixed in location on or within apatient's body via an adhesive, a tissue fixation screw, helix, barband/or hook, a suction source, an inflatable balloon, an expandablestructure, and/or via physical pressure.

One embodiment of the present invention includes an esophageal devicethat comprises one or more sensors, e.g., receiving sensor coils, whichallow determination of the location of the esophageal device in 3-Dspace. One embodiment of the present invention includes atrans-esophageal device, e.g., a trans-esophageal imaging device,trans-esophageal stimulation device and/or ablation device, whichcomprises one or more sensors, e.g., receiving sensor coils, which allowdetermination of the location of the trans-esophageal device in 3-Dspace.

One embodiment of the present invention includes a tracheal device thatcomprises one or more sensors, e.g., receiving sensor coils, which allowdetermination of the location of the tracheal device in 3-D space. Oneembodiment of the present invention includes a trans-tracheal device,e.g., trans-tracheal imaging device, trans-tracheal stimulation deviceand/or trans-tracheal ablation device, which comprises one or moresensors, e.g., receiving sensor coils, which allow determination of thelocation of the trans-tracheal device in 3-D space.

One embodiment of the present invention includes a vascular device thatcomprises one or more sensors, e.g., receiving sensor coils, which allowdetermination of the location of the vascular device in 3-D space. Oneembodiment of the present invention includes a trans-vascular device,e.g., trans-vascular imaging device, trans-vascular stimulation deviceand/or trans-vascular ablation device, which comprises one or moresensors, e.g., receiving sensor coils, which allow determination of thelocation of the trans-vascular device in 3-D space.

One embodiment of the present invention includes a guiding device, e.g.,a guiding catheter device, which comprises one or more sensors, e.g.,receiving sensor coils, which allow determination of the location of theguiding device in 3-D space. One embodiment of the present inventionincludes a catheter-like insert device, which may be inserted throughthe lumen of a larger catheter device, the catheter-like insert devicecomprising one or more sensors, e.g., receiving sensor coils, whichallow determination of the location of the catheter-like insert devicein 3-D space.

One embodiment of the present invention includes a stimulation devicethat comprises one or more sensors, e.g., receiving sensor coils, whichallow determination of the location of the stimulation device in 3-Dspace. One embodiment of the present invention includes a nervestimulation device, e.g., a vagal nerve stimulation device, whichcomprises one or more sensors, e.g., receiving sensor coils, which allowdetermination of the location of the nerve stimulation device in 3-Dspace.

One embodiment of the present invention includes a tissue-engagingdevice that comprises one or more sensors, e.g., receiving sensor coils,which allow determination of the location of the tissue-engaging devicein 3-D space. One embodiment of the present invention includes a tissuedissection device, which comprises one or more sensors, e.g., receivingsensor coils, which allow determination of the location of the tissuedissection device in 3-D space. One embodiment of the present inventionincludes a tissue retraction device, which comprises one or moresensors, e.g., receiving sensor coils, which allow determination of thelocation of the tissue retraction device in 3-D space.

One embodiment of the present invention may comprise one or more tissueablation devices and/or mapping devices, for example, disclosed in U.S.patent application Ser. No. 10/853,594 filed May 25, 2004, Ser. No.11/040,663 filed Jan. 21, 2005, Ser. No. 11/128,786 filed May 13, 2005,Ser. No. 11/142,954 filed Jun. 2, 2005, Ser. No. 11/143,400 filed Jun.2, 2005, Ser. No. 11/143,128 filed Jun. 2, 2005, Ser. No. 11/143,399filed Jun. 2, 2005, and Ser. No. 11/155,699 filed Jun. 17, 2005. Thesepatent applications are assigned to Medtronic, Inc. and are incorporatedherein by reference in their entirety.

A medical procedure according to one embodiment of the present inventionmay be a non-invasive, minimally invasive and/or invasive procedure. Inone embodiment, the medical procedure may entail a port-access approach,a partially or totally endoscopic approach, a sub-xyphoid approach, asternotomy approach and/or a thoracotomy approach. The medical proceduremay include the use of various robotic, imaging systems, and/or guidancesystems. The medical procedure may be a procedure comprising the heart.Alternatively, the medical procedure may be a procedure comprisinganother organ of the body. The medical procedure may be a procedurecomprising more than one organ of the body. In one embodiment, on ormore medical devices of the present invention may be positioned andused, for example, through a sternotomy, through a thoracotomy thatavoids the sternal splitting incision of conventional cardiac surgery,through a mini-thoracotomy, through a sub-xyphoid incision,percutaneously, transvenously, arthroscopically, endoscopically, forexample, through a percutaneous port, through a stab wound or puncture,through a small or large incision, for example, in the chest, in thegroin, in the abdomen, in the neck or in the knee, or in combinationsthereof. In one embodiment, on or more medical devices of the presentinvention may be guided into a desired position using various imagingand/or guidance techniques as described herein.

FIG. 20 shows an ablation device 410 which may be used according to oneembodiment of the present invention. Ablation device 410 comprises anelongated member or shaft 440, which couples an ablating tip 442, whichcomprises one or more ablating elements, to a handle 420 that may beheld and manipulated by a surgeon. In one embodiment, ablation device410 comprises one or more sensors. For example, shaft 440 of ablationdevice 410 may comprise one or more sensors 430, e.g., one or moresensor coils, thereby allowing the device to be tracked within apatient's body via an image guidance device or system as describedherein. The ablation device may include a fluid source, an indifferentelectrode and an ablating power source, e.g., an RF energy source.

In one embodiment, once the target site (e.g., right atrium, leftatrium, epicardial surface, endocardial surface, etc.) is accessible,the surgeon guides the ablating tip 442 of the ablation device 410 tothe target site. The surgeon may use pre-acquired images, as describedabove, and an image guidance system, as described above, to help guidethe ablating tip 442 into position. Once the ablating tip 442 is locatedin a desired position, the ablating tip 442 is then energized, ablating(or for some applications, cauterizing) the contacted tissue. A desiredlesion pattern may then be created (e.g., portions of a known “Maze”procedure) by guiding the tip in a desired fashion along the targetsite, for example. The image guidance system of the present inventionmay allow a minimally invasive ablation procedure to occur without aphysician having direct visualization. The image guidance systemdescribed herein may enable a physician to know the proximity of anablating member to a cardiac structure, e.g., a coronary artery, and/orextra-cardiac structures, e.g., an esophagus, prior to ablating. Theimage guidance system of the present invention may allow an ablationlesion path or line that a physician creates to be marked on a cardiacimage, thereby helping to guide the physician in creating a completelesion set of an ablation procedure.

FIG. 21 shows a mapping device 310 which may be used according to oneembodiment of the present invention. Mapping device 310 comprises anelongated member or shaft 340, which couples a mapping tip 342, whichmay comprise one or more mapping electrodes, to a handle 320 that may beheld and manipulated by a surgeon. In one embodiment, mapping device 310comprises one or more sensors. For example, shaft 340 of mapping device310 may comprise one or more sensors 330, e.g., one or more sensorcoils, thereby allowing the device to be tracked within a patient's bodyvia an image guidance device or system, as described herein. The mappingdevice may include a diagnostic device and an indifferent electrode.

In one embodiment of the present invention, it may be desirable toidentify an origination point of an undesired electrical impulse of theheart prior to ablation. Mapping may be accomplished by placing one ormore mapping electrodes into contact with the tissue in question.Mapping of tissue may occur by placing one or more mapping electrodesinto contact with the endocardial surface of the heart and/or theepicardial surface of the heart. In one embodiment, once the target site(e.g., right atrium, left atrium, epicardial surface, endocardialsurface, etc.) is accessible, the surgeon guides the mapping tip 342 ofthe mapping device 310 to the target site. The surgeon may usepre-acquired images, as described above, and an image guidance system,as described above, to help guide the mapping tip 342 into position.Once the mapping tip 342 is located in a desired position, mapping mayoccur.

Mapping may occur on isolated or non-isolated tissues on or near theleft atrium for lesion evaluation following an ablation procedure, forexample. Mapping may also allow marking and cataloging of sites whereautonomic ganglia are found. In cases where biventricular pacing leadsare to be placed, the mapping device may be guided into variouslocations to identify the optimal pacing site. The optimal pacing sitemay then be marked on a previously acquired cardiac image. The locationof various structures, e.g., a phrenic nerve, may be marked on apreviously acquired image as well when it is located by amapping/stimulation device according to one embodiment.

FIG. 22 shows an ablation device 500 which may be used according to oneembodiment of the present invention. Ablation device 500 generallycomprises an elongated handle assembly 510 having a jaw assembly 590mounted at handle distal end 515, a trigger 520 intermediate the handleproximal and distal ends 595 and 515. The trigger 520 is employed tomove the jaws of the first or lower jaw assembly 540 with respect to thesecond or upper jaw assembly 530 of the jaw assembly 590 together tocompress tissue therebetween to allow for creation of a linear ablationlesion to occur by emitting ablative energy from ablating jaw members530 and 540.

The upper jaw and lower jaw assemblies 530 and 540 have opposed upperand lower jaws 535 and 545, respectively, each comprising an ablatingelement, e.g., an electrode assembly. The swivel assembly 550 providesthe physician with the opportunity to position the jaw assembly 590 in avariety of orientations relative to the handle 510, to facilitateplacing the 535 and 545 jaws against tissue to form desired lines oflesions, e.g., the heart wall in performance of a Maze procedure or amodified Maze procedure. In one embodiment, the physician may manuallygrasp and rotate the swivel assembly 550 and the jaw assembly 590 toprovide a roll adjustment R, preferably through an arc of at least 300degrees, relative to the axis of the distal end 515 of the handle 510through interaction of components of the handle and swivel assembly. Inone embodiment, the physician may manually grasp the jaw assembly 590and adjust it in pitch P relative to the swivel assembly 550 through theinteraction of components of the jaw assembly 590 and the swivelassembly 550. In one embodiment, the available are of pitch P adjustmentextends over at least 90 degrees. Moreover, the upper and lower jaws 535and 545 may be malleable. In one embodiment, ablation device 500comprises one or more sensors. For example, jaw assembly 590 maycomprise on or more sensors 580, e.g., one or more sensor coils, therebyallowing the device jaws to be tracked within a patient's body via animage guidance device or system as described herein. The ablation devicemay include a fluid source and an ablating power source, e.g., an RFenergy source.

In one embodiment, once the target site (e.g., right atrium, leftatrium, epicardial surface, endocardial surface, etc.) is accessible,the surgeon guides the jaw assembly 590 of the ablation device 500 tothe target site. The surgeon may use pre-acquired images, as describedabove, and an image guidance system, as described above, to help guidethe jaw assembly 590 into position. The image guidance system may allowa physician to verify that the ablating elements of the jaw assembly arepositioned properly prior to ablation. Once the jaw assembly 590 islocated in a desired position, the ablating elements of jaw assembly 590are then energized to ablate (or for some applications, cauterize) thecontacted tissue. A desired lesion pattern may then be created (e.g.,portions of a known “Maze” procedure) by guiding the jaw assembly intoone or more desired positions. The image guidance system of the presentinvention may allow a minimally invasive ablation procedure to occurwithout a physician having direct visualization. The image guidancesystem described herein may enable a physician to know the proximity ofan ablating member to a cardiac structure, e.g., a coronary artery,and/or extra-cardiac structures, e.g., an esophagus, prior to ablating.The image guidance system of the present invention may allow an ablationlesion path or line that a physician creates to be marked on a cardiacimage, thereby helping to guide the physician in creating a completelesion set of an ablation procedure. Multiple sensors, e.g., sensorcoils, incorporate into ablation device 500 may allow a physician totell if the ablation jaws are bent to either side and/or if the jaws areskewed. The line of tissue clamped between the jaws may be marked on acardiac image to record the lesion location.

One embodiment of a method according to the present invention isoutlined in FIG. 23. An imaging device acquires one or more images, asdescribed herein, of a patient's anatomy of interest at 610. Next animage guidance system comprising reference markers, as described herein,is used to correlate the acquired image(s) with the patient's anatomy at620. A medical device, e.g., an ablation device, comprising one or moreimage guidance sensors is then inserted into the patient at 630. Themedical device is then guided into a desired position, e.g., adjacentcardiac tissue, using the image guidance system at 640. A medicalprocedure, e.g., an ablation procedure comprising the ablation ofcardiac tissue, is performed at 650. The medical device is removed fromthe patient at 660.

As described herein, an imaging device may be used to acquire an image(or images) of an anatomy of interest, or an anatomical area ofinterest, within the patient. Examples of types of imaging devices thatmay be used in various embodiments of the invention include ultrasound,CT, MRI, PET, fluoroscopy, and echocardiography devices. The acquiredimage may be registered to the patient, which may allow for correlationof the acquired image with the anatomy of the patient, for example, toprovide real-time (or near real-time) monitoring and guidance of amedical device with respect to a patient's anatomy. An image guidancesystem according to an embodiment of the invention may provide a visualdisplay of the locations or positions of medical devices (or portions ofmedical devices, such as sensors) relative to one or more of theacquired images, for example, during medical procedures such as cardiacablations.

In some embodiments, the method outlined generally in FIG. 23 includesguiding the ablation device to an energy delivery location within thepatient. Suitable energy delivery locations within the patient includeareas within the patient's body that are relatively easily accessible,and which may allow placement of the ablation device (or a portion ofthe ablation device) so that it is disposed a known or appropriatedistance from a target area of tissue. For example, in some embodiments,the energy delivery location may be selected from any of the following:the esophagus, the trachea, or bronchi of the lungs of the patient. Suchlocations may, for example, be suitable for delivering HIFU energy to ananatomy of interest in the patient, such as cardiac tissue located adistance from the energy delivery location. The anatomy of interest mayinclude cardiac tissue to be ablated to treat atrial fibrillation incertain embodiments, for example, according to a Maze procedure. HIFUenergy may be emitted from a HIFU emitting member of the ablation devicedisposed at the energy delivery location to the cardiac tissue to beablated according to a Maze procedure according to certain embodimentsof the invention. The anatomy of interest may include cardiac tissuenear the pulmonary veins, for example. Certain embodiments may includeguiding at least a portion of an ablation device (such as a HIFUemitting member) to the energy delivery location using transesophagealechocardiography (TEE).

The distal portion comprising an ultrasound emitting member of oneembodiment of a medical device according to the present invention isshown in FIG. 24. The ablation device shown in FIG. 24 may be used intrans-esophageal ultrasound ablation of cardiac tissue, for example. Inone embodiment of the present invention, the flexible tube or shaft hasa length and rigidity sufficient for manipulating the distal portion ofthe device or probe head attached to the distal end of the flexible tubeor shaft down within the esophagus of a patient. The proximal end of theflexible tube may reside outside of the patient's body while the distalend resides within the patient's body, e.g., the patient's esophagus.According to one embodiment of the present invention, an array oftransducer elements as shown in FIG. 25 may be used in trans-esophagealultrasound ablation of cardiac tissue. FIG. 25 shows a 2-D 64-elementsparse (spatially sampled from 15-by-13 elements) tapered phased arraywith total size of approximately about 20.72×10.24 mm² with theproportions of ceramic and matching layers. FIGS. 26a and 26b show thesimulation results of the ultrasound field of the normalized intensityfor on-axis focusing with the focal point aimed at (a) (0, 0, 40) mm andoff-axis focusing at (b) (10, 10, 40) mm plotted as a contour withlevels indicated at 0, −1, −2, −3, −6, −9 and −12 dB. According to thesimulation results, the transducer array of FIG. 25 may producewell-defined zones for both on-axis and off-axis focusing and reducedgrating lobes, which can cause an unwanted ablation in tissue.

In one embodiment of the present invention, the transducer design is a2-D phased array with flat tapered transducer elements. The spatiallysparse array uses 64 active elements operating at frequency of 1.6 MHzsampled from 195 (15-by-13) rectangular elements. The ablating probehead, which may be MRI-compatible, includes a housing, e.g., 19 mm indiameter, an acoustic window or membrane, e.g., a latex membrane, toprotect the transducer elements and to ensure the delivery of maximumacoustical power from the transducer elements to the ablation target(s),cooling pipes/lumens, connectors and a flexible insertion tube, as shownin FIGS. 27 and 28. In one embodiment of the present invention, the mainbody may have a length of approximately about 67 mm and a diameter ofapproximately about 18 mm.

In one embodiment of the present invention, the acoustic window maycomprise a latex membrane. The membrane helps to create a bolus offluid, e.g., water, delivered by the cooling pipes/lumens around thetransducer elements. The fluid helps to provide a good coupling betweenthe device and tissue, e.g., the esophageal wall. It is desirable thatthe material used to create the acoustic window have similar acousticimpedance as does the fluid surrounding the transducers, so as to beacoustically transparent. It should avoid extreme refraction of theultrasound beam due to the different propagation speed between thecooling fluid surrounding the transducers and the window, and the windowand the esophageal wall, for example, which may cause unwanted heatingaround the esophageal wall. To simulate the refraction of the ultrasoundbeam due to the acoustic window, a half-cylindrical window with TPX®(Z=1.78 MRayls, c=2170 m/s) was modeled with water (Z=1.5 MRayls, c=1500m/s) and Tissue (Z=1.5 MRayls, c=1500 m/s) and refracted anglesaccording to the height of each element was calculated, as shown inFIGS. 29 and 30. The resulting ultrasound rays are illustrated in FIGS.31a and b wherein the thickness of the window wall is 2 mm and 1 mm,respectively. As shown in FIGS. 30 and 31, the thickness of the acousticwindow is a factor of the ultrasound beam when two mediums havedifferent speed of sound though they have similar impedance. Becauseuncontrolled heating in virtue of the extreme refracted angles ofultrasound beam depicted in FIG. 31a can cause damage to the esophagealwall, for example, the thickness of the window must be carefullyselected.

In one embodiment of the present invention, the transducer array maycomprise ceramic: PZT-8 (Z=MRayls), Insulcast® 501 and silver epoxy(Z=7.14 MRayls), coaxial cable and epoxy. The probe head housing maycomprise polyurethane and/or Delrin® for the housing body, acousticallytransparent polyurethane and/or TPX® for the acoustic window, amachinable glass ceramic, e.g., Macor® and/or Delrin® for the ceramicsupporter, polyurethane and/or Delrin® for the nose-corn and connectorsand polyurethane (spray) and/or sealing tape for sealing. The flexibletube may comprise polyurethane, silicone, TPFE and/or Tygon tubing. Thecooling pipes may comprise copper within the probe head and rubberwithin the flexible tube.

In one embodiment of the present invention, the device may compriseelectrical impedance matching circuits. For example, individual LCcircuits may be built for each of the transducer elements to match eachone to a common value, e.g., 50 Ω<0°. An impedance matching equivalentcircuit is shown in FIG. 32. The impedance of the matching circuit maybe adjusted by varying the value of the capacitance and the number ofturns of coils.

In one embodiment of the present invention, an amplifier system may beused to power or drive the transducer array. The power source oramplifier system may be a multi-channel high power, ultrasoundphased-array transducer driver for 64 elements which may be capable ofdelivering 50 W per channel with ±1° phase resolution each.

In one embodiment of the present invention, the transducer array may befabricated from piezoelectric ceramic, PZT-8. The ceramic material maybe diced in 20.70 mm×10.24 mm and lapped to a thickness of 1.437 mmcorresponding to the resonance frequency of 1.6 MHz. The ceramic has theelectrode surfaces coated with chromium and gold sputtering and thinoxidized silver matching layer on the surface that radiate ultrasoundinto the tissue. The thickness and material of the matching layer may beselected based on the solution to a three-layer (transducer, matchinglayer and tissue) problem, which ensures the required maximum powertransfer. The matching layer in one embodiment is a 2:1, epoxy ofInsulcast® 501 to silver powder mixture. FIGS. 33a, b and c show viewsof a transducer array at different stages of the fabrication process.FIG. 33a shows a lapped, gold-sputtered, and matching layer-attachedpiezoceramic (20.70×10.24 mm²). FIG. 33b shows a diced array imbedded inthe frame. The ceramic was completely diced through its thickness toform a 64-element sparse phased array and attached securely to the frameusing silicone with a primer. FIG. 33c shows a wired array following thesoldering of wires to the ceramic elements. In one embodiment of thepresent invention, the elements are soldered to MRI compatible, 42 AWG,30 pF/ft miniature coaxial cables, each 2.5 meters long. The cables areused to connect the transducer elements of the phased array to theamplifier system. In one embodiment, a micro-tip soldering pin at lowtemperature (less than the Curie temperature of PZT-8) was used tosolder the core of each coaxial cable to its designated element. Forthis process, the soldering temperature was kept below 500° F. toprevent any damage to the piezoelectric ceramic.

It will be appreciated by those skilled in the art that while theinvention has been described above in connection with particularembodiments and examples, the invention is not necessarily so limited,and that numerous other embodiments, examples, uses, modifications anddepartures from the embodiments, examples and uses are intended to beencompassed by the claims attached hereto. The entire disclosure of eachpatent and publication cited herein is incorporated by reference in itsentirety, as if each such patent or publication were individuallyincorporated by reference herein.

What is claimed is:
 1. An ablation device for ablating tissue within apatient, comprising: a two-dimensional array of transducer elementsincluding a plurality of transducer elements, the two-dimensional arrayof transducer elements configured to deliver high intensity focusedultrasound (HIFU) energy, wherein the transducer elements have a taperand further wherein the transducer elements positioned more centrally inthe two-dimensional array are larger than the transducer elementspositioned more peripherally in the two-dimensional array.
 2. Theablation device of claim 1, wherein the taper comprises a gradualreduction in size of the transducer elements from a center of thetwo-dimensional array to a periphery of the two-dimensional array. 3.The ablation device of claim 1, wherein the taper is configured suchthat high intensity focused ultrasound (HIFU) energy delivered from thetwo-dimensional array is at least approximately three decibels greaterintensity at a focus zone in comparison to a grating lobe.
 4. Theablation device of claim 1, wherein each of the transducer elements hasan approximately equal impedance to each other ones of the transducerelements.
 5. The ablation device of claim 4, further comprising animpedance match circuit operatively coupled to the transducer elementsand providing, at least in part, the approximately equal impedance ofeach of the transducer elements to each other ones of the transducerelements.
 6. The ablation device of claim 5, wherein the impedance isapproximately fifty ohms at a temperature of zero degrees centigrade. 7.The ablation device of claim 4, further comprising: an acoustic membranehaving an acoustic impedance and positioned with respect to thetwo-dimensional array; and a fluid contained within the ablation device,at least in part, by the acoustic membrane, the fluid having a fluidimpedance; wherein the acoustic impedance of the acoustic membrane isapproximately equal to the acoustic impedance of the fluid.
 8. Theablation device of claim 7, wherein the acoustic membrane is comprisedof a material having a thickness, the thickness of the acoustic membranebeing a function of a difference between a speed of sound through thematerial and a speed of sound through the fluid to reduce a refractionof said high intensity focused ultrasound (HIFU) energy through thematerial.
 9. The ablation device of claim 1: wherein the two-dimensionalarray further comprises a number of grid elements and wherein thetwo-dimensional array has a number of the transducer elements; whereinthe transducer elements of the two-dimensional array are spatiallysparse due to the number of grid elements being greater than the numberof transducer elements.
 10. The ablation device of claim 1, wherein thetwo-dimensional array of transducer elements is a two-dimensional phasedarray of transducer elements.
 11. A method for ablating tissue of apatient, comprising: delivering high intensity focused ultrasound (HIFU)energy from a two-dimensional array of transducer elements to tissue ofthe patient, wherein the two-dimensional array of transducer elementsincludes a plurality of transducer elements, the two-dimensional arrayof transducer elements having a taper and further wherein the transducerelements positioned more centrally in the two-dimensional array arelarger than the transducer elements positioned more peripherally in thetwo-dimensional array.
 12. The method of claim 11, wherein the highintensity focused ultrasound (HIFU) energy delivered from thetwo-dimensional array of transducer elements is at least approximatelythree decibels greater intensity at a focus zone in comparison with agrating lobe.
 13. The method of claim 11, wherein each transducerelement of the two-dimensional array of transducer elements isindependently actuatable, and wherein the focusing step comprisesindependently actuating each transducer element.
 14. The method of claim11, wherein the delivering high intensity focused ultrasound (HIFU)energy to tissue of the patient includes focusing the high intensityfocused ultrasound (HIFU) energy to a focus zone at a predetermineddistance from the array of transducer elements.
 15. The method of claim11, wherein each of the transducer elements has an approximately equalimpedance to each other ones of the transducer elements.
 16. The methodof claim 11, wherein each transducer element of the two-dimensionalarray of transducer elements is selectively actuatable to allow forelectronic steering of the high intensity focused ultrasound (HIFU)energy.
 17. The method of claim 11, wherein the taper comprises agradual reduction in size of the transducer elements from a center ofthe two-dimensional array to a periphery of the two-dimensional array.18. The method of claim 11, wherein the two-dimensional array oftransducer elements is a two-dimensional phased array of transducerelements.
 19. The method of claim 11: wherein the two-dimensional arrayfurther comprises a number of grid elements and wherein thetwo-dimensional array has a number of the transducer elements; whereinthe transducer elements of the two-dimensional array are spatiallysparse due to the number of grid elements being greater than the numberof transducer elements.